Why is Genome Scan important?
Personal genomics has immediate importance to health care: A personal genome will provide at a minimum the information content of a large number of individual genetic tests. In some cases this information will predict risk for serious disease that will encourage follow-on tests or medical interventions, in others it will encourage long term surveillance for signs of disease development, but a great deal of the information will be neutral or of uncertain significance. Two high priorities for the field of personal genomics are to develop the education and support services that will enable individuals to understand and use their personal genomic information, and to raise awareness of the implications of personal genomics for doctors, medical educators, medical economists, insurers, and policy makers. Stakeholders in the field of personal genomics must actively foster collaborations that will develop approaches to addressing these implications.

What does Genome Scan tell?

The genome scan reveals:

• An analysis of genetic risk factors for 42 traits and conditions
• The complete Ancestry Scan
• Regular updates – as new discoveries are made
• Tools to compare your results to those of friends and family
  Advanced features – so you can explore your genome in detail
  

What are the conditions it assess?

The conditions it covers are categorized into these main groups:

1. Cancers:
   Basal Cell Carcinoma
   Bladder Cancer
   Breast Cancer
   Chronic Lymphocytic Leukemia
   Colorectal Cancer
   Lung Cancer
   Prostate Cancer
   Thyroid Cancer
   
2. Blood:
   ABO Blood Types
   Chronic Lymphocytic Leukemia
   Hemochromatosis
   Venous Thromboembolism
   Warfarin Metabolism
   
3. Bones, joints and muscles:
   Gout
   Rheumatoid Arthritis
   Statin Induced Myopathy
   
4. Brain and nerves:
   Alzheimer’s Disease
   Essential Tremor
   Multiple Sclerosis
   Nicotine Dependence
   Restless Legs Syndrome
   
5. Eyes and vision:
   Age Related Macular Degeneration
   Exfoliation Glaucoma
   Eye Color
   
6. Lungs and breathing:
   Asthma
   Lung Cancer
   Nicotine Dependence
   
7. Heart and circulation:
   Abdominal Aortic Aneurysm
   Atrial Fibrillation
   Heart Attack
   Intracranial Aneurysm
   Peripheral Arterial Disease
   Venous Thromboembolism
   
8. Digestive and metabolic system:
   Alcohol Flush Reaction
   Bitter Taste Perception
   Celiac Disease
   Colorectal Cancer
   Crohn’s Disease
   Gallstones
   Lactose Intolerance
   Obesity
   Type 1 Diabetes
   Type 2 Diabetes
   Ulcerative Colitis
   
9. Skin, hair and nails:
   Basal Cell Carcinoma
   Male Pattern Baldness
   Psoriasis
   

Basal Cell Carcinoma

Basal cell carcinoma is the most common type of skin cancer. Skin cancer is the most prevalent type of cancer in human beings and occurs in three main forms: melanoma, basal cell carcinoma and squamous cell carcinoma. Each of these takes its name from the type of skin cell in which it originates. The latter two, basal cell carcinoma and squamous cell carcinoma, are often referred to as non-melanoma skin cancers.

Most basal cell cancers are found on sun-exposed skin
Basal cell carcinomas are malignant tumors that originate in the basal cells lining the inner part of the epidermis. They are the most common form of skin cancer, accounting for 75% of all diagnosed cases. It is estimated that about one million new cases are diagnosed in the US each year. This type of skin cancer usually appears on areas of the skin most exposed to the sun (head, face, neck, hands and arms).

Exposure to UV-rays of the sun are the main risk factor
Regular exposure to the ultraviolet (UV) rays of the sun increases the risk of developing all types of skin cancer, including basal cell carcinoma. Exposure to UV rays from the sun is mainly dependent on how far away from the equator one lives. In the far north (e.g. in places such Iceland, Finland and Alaska) there is relatively little UV radiation from the sun and the risk of too much exposure is low, whereas those living in northern Australia, Florida, India and Ethiopia are much more highly exposed. Exposure to UV radiation on tanning beds also increases the risk of developing basal cell carcinoma.

An interaction of genes and environment causes BCC
Given the same level of exposure to UV radiation as people with a dark complexion, individuals with pale skin, with red or blonde hair and blue or green eyes and who are tan-resistant and burn easily are particularly at risk of developing basal cell carcinoma. This is thought to be due to the fact that a light complexion provides less protection from UV radiation than a dark complexion. Because skin, hair and eye color are by and large genetically determined, the risk of developing basal cell carcinoma from UV radiation exposure therefore results from a mixture of genetic and environmental factors. However, there are also genetic risk factors for basal cell carcinoma that appear to act independently of exposure to UV radiation.

Genetics contribute to the risk of BCC
Scientists at deCODE genetics have identified genetic variants that confer a significant risk of developing basal cell carcinoma in people of European descent. Two variants are located on chromosome 1 and one variant on each of the following chromosomes; 5, 7, 9, and 12. These variants are not known to affect the hair, eye and skin color traits that are associated with poor UV protection. Therefore they probably represent risk factors that are separate from and therefore additional to UV radiation exposure.

deCODEme can calculate your genetic risk of developing BCC
The deCODEme Complete Scan identifies these six variants and provides an interpretation of the associated risk for the development of basal cell carcinoma for individuals of European descent. At this time risk information is not available for other ethnicities.

Risk factors for BCC

• Ultraviolet (UV) radiation: UV exposure is thought to be the major risk factor for basal cell carcinoma and most other skin cancers. This is because UV can damage the DNA carried by skin cells causing them to grow and divide uncontrollably. Sunlight and tanning beds are the main sources of UV radiation. People with excessive and unprotected exposure to light from these sources are at greater risk for all kinds of skin cancers. Studies also suggest that exposure at a young age is an added risk factor.
• 
  Complexion: Hair, eye and skin color are determined by the amount and type of melanin produced by cells called melanocytes. Melanin is a special form of pigment that absorbs light and provides protection from the damaging effects of UV radiation. People with fair skin, freckles and red or blonde hair have less light-absorbing melanin in their skin and hence have a higher risk of developing skin cancer.
• 
  Gender and age: Men are 50% more likely to develop basal cell carcinoma than women. This is thought to be mainly because men are more exposed to the sun (outdoor labor) less aware of the need for UV protection. Basal cell carcinoma is more common in both sexes after the age of 40.
• 
  Family history: Not surprisingly, family history plays a role in the development of skin cancers. This is partly because complexion is largely genetically determined. At the same time, family members also tend to live in the same areas with comparable UV radiation exposure. Genetic variants have been found to increase risk for certain skin cancers, mostly through their effect on lightening skin complexion.

Avoiding sun-burn is an important prevention strategy
The best known way to lower the risk of any skin cancer is to avoid sun-burn and limit exposure to the sun and other sources of UV radiation, including tanning beds and sun lamps.

Early detection is key to successful treatment of BCC
If detected early, basal cell carcinoma is comparatively easy to treat. However, 5-10%of basal cell carcinoma tumors can be resistant to treatment or can damage the skin around them, sometimes invading bone and cartilage. Fortunately, however, basal cell carcinoma has an extremely low rate of spreading to other parts or organs of the body (metastasis), and although it can result in scarring it is usually not life threatening.

Routine skin-examinations important for early diagnosis
As early detection of basal cell carcinoma is the key to successful treatment, it is important to recognize what basal cell cancer looks like and perform regular self-examinations of your skin, especially if you are at increased risk for developing this type of skin cancer. If you observe any unusual change in your skin such as a bump, a sore that doesn’t heal, or an area with different color or texture than the skin around it, consult your physician.

A variety of treatment methods exist for BCC
There is no single best method to treat all skin cancers. The method of choice is determined by many factors, including the location, type, size, whether it is a first-time tumor or a recurrent one, and the health and preference of the patient.

Continue skin-examinations after successful treatment
Patients who have had one occurrence of basal cell skin cancer have a 40% greater risk of developing new tumors in the next five years. The tumors can recur even when they appear to have been adequately treated. Therefore, even after successful treatment of basal cell carcinoma, patients should perform skin self examinations routinely and continue to see their physician for regular follow-up visits for several years to make sure that the growth has not recurred and also to check for new skin cancers.

Bladder Cancer

Bladder cancer is more common in men than in women
It is estimated that nearly 70,000 individuals will be diagnosed with bladder cancer in the United States during 2008 and that approximately 20% of them will die of the disease. Bladder cancer is more common in men than in women and more common among white individuals of European descent than African Americans, Hispanics, and Asians. In the United States, approximately 1 in 24 men will be diagnosed with bladder cancer during his lifetime whereas only 1 in 77 women will develop the disease. If discovered and treated early, bladder cancer has a high rate of cure.

Genetics contribute to the risk of bladder cancer
Both genetic and environmental factors contribute to the risk of developing bladder cancer. Bladder cancer has been linked to exposure to various types of toxic substances such as cigarette smoke and industrial chemicals but genetic factors also play a significant role. Scientists at deCODE genetics and others have discovered four genetic variants that increase the risk of developing bladder cancer; one on chromosomes 3 and 5 and two on chromosome 8.

deCODEme calculates your genetic risk of bladder cancer
The deCODEme Complete Scan and the deCODEme Cancer Scan identify all three genetic variants and provide interpretation of the associated risk of developing bladder cancer in white individuals of European ancestry. Currently no risk data for these variants are available for people of other ethnicities.

Risk factor for bladder cancer

As the exact cause of bladder cancer is still unknown, several risk factors have been established:

• Smoking is the strongest risk factor for bladder cancer. Smokers develop bladder cancer twice as often as non-smokers.
• Chemical exposure. Painters, hairdressers, machinists, printers, and truck drivers are among those whose exposure to various chemicals increases their risk for bladder cancer. Others include individuals who work with aromatic amines, a group of chemicals that are used in the production of rubber, printing materials, textiles, and paint products as well as in the treatment of leather. Arsenic in drinking water has also been linked to an increased risk of the disease.
• Ethnicity. White individuals of European origin are twice as likely to develop bladder cancer as are African Americans and Hispanics. Asians have the lowest rate of bladder cancer.
• Age. The risk of bladder cancer increases with age.
• Gender. The incidence of bladder cancer in men is more than three times greater than in women.
• Family history. Those with a first-degree relative who has developed bladder cancer are at greater risk.
• Other risk factors include having a history of chronic bladder infection, bladder birth defects and not drinking enough liquids.
• Reoccurrence. Bladder cancer can reoccur. Those who have had it once are at a greater risk of developing it a second time.
  

Not smoking is an important prevention strategy
The most important preventive measures are to refrain from smoking and to take recommended caution with chemicals. Drinking plenty of liquids, especially water, dilutes toxic substances that may be found in a concentrated form in urine and flushes them out of the bladder more quickly. Since arsenic is known to affect bladder cancer, household wells and other private water supplies should be tested for high arsenic levels. A diet rich in fruits and vegetables may reduce the risk of bladder cancer.

If discovered and treated early, bladder cancer has a high cure-rate
Treatment of bladder cancer depends on a number of factors, including the type and stage of the cancer, overall health and treatment preferences. Most people undergo surgery to remove the cancer and surrounding tissue. If the tumor has invaded nearby tissue, the whole bladder may be removed and reconstructive surgery performed so that urine can be expelled. If further treatment is required, it may include chemotherapy, radiation and/or immunotherapy (aimed at stimulating the immune system to fight the remaining cancer cells).

Breast Cancer

Breast cancer is the most common type of cancer among women
In the United States, approximately one in twelve women will be diagnosed with breast cancer during her lifetime. Most women have a friend, a co-worker, or a close relative who has experienced breast cancer first-hand and not surprisingly, many women fear this disease the most.

Early diagnosis increases chances of successful treatment
The good news is, that if diagnosed early, breast cancer can be treated very successfully. Over 90% of women diagnosed in the earliest stages of breast cancer go on to lead normal, healthy lives after treatment. Early diagnosis of breast cancer and treatment are crucial in the management of breast cancer.

Genetic factors contribute to the risk of breast cancer
Genetic factors contribute significantly to the risk of developing breast cancer. You may have heard of the high risk genetic variants associated with breast cancer and ovarian cancer found in the BRCA1 and BRCA2 genes. Although much researched and widely known, these are very rare variants, present in only 2-5% of breast cancer patients.

Common genetic variants play a role in most breast cancer cases
There are several, more common, genetic variants that play a role in a much larger proportion, if not all breast cancer cases, but carry less risk than the BRCA1 and BRCA2 variants. Currently, eleven common genetic variants are known to increase the risk of developing breast cancer in people of European descent: two on chromosomes 2 and 5 and one on each of the following chromosomes: 1, 3, 8, 10, 11, 14 and 16. A variant in the ESR1 gene on chromosome 6 contributes to the risk of breast cancer in East Asians but not people of European descent.

Knowing your family history is not enough
While each of the common genetic variants on its own, is associated with only a small increase in breast cancer risk, if a woman inherits many, or all of these variants, the combined risk can be high (up to an almost fourfold risk compared to the general population). Tracing combinations of these common breast cancer risk variants through family history may however be difficult.

Herein lies the informative value of the deCODEme genetic scan; Empowered by the knowledge of your genetic risk of breast cancer, you may become better prepared to select, along with your doctor, the many preventive actions and lifestyle choices now known to reduce the risk of developing breast cancer.

deCODEme calculates your genetic risk for breast cancer
The deCODEme Complete Scan identifies the 11 common genetic variants listed above and provides interpretation of their associated risk for developing breast cancer in women of European descent. For women of East-Asian descent the deCODEme Genetic Scan calculates genetic risk associated with the five variants listed above that have been validated in this population, including the ESR1 gene variant. At the present time no risk estimation data are available for people of other ethnicities for the common variants included in the deCODEme genetic risk scans.

Please note that the deCODEme genetic scan does not test for the rare BRCA1 or BRCA2 variants. If you have close relatives with early onset breast cancer or ovarian cancer, the possibility of a BRCA mutation should be discussed with your doctor.

What is breast cancer?
Breast cancer is an uncontrolled growth of breast cells
Breast cancer, like other cancers, is cell growth gone haywire. Breast cancer can be defined as a malignant tumor that starts from breast cells and usually begins either in the cells of the breast lobules, which are the milk-producing glands, or the ducts, the passages through which milk flows from the lobules to the nipple. The different types of cells in these tissues give rise to different types of breast cancer, depending on where in the breast the cancer originates.

If untreated, breast cancer can spread to other parts of the body
Over time, and if untreated, breast cancer cells may invade the surrounding healthy breast tissue and reach the nearby underarm lymph nodes that connect with the body´s entire lymphatic system. If breast cancer cells make their way to the lymph nodes, or invade blood vessels, they soon find their way to other parts of the body and can cause cancer growth there, for example in the bones or liver. This is a serious cancer development known as metastasis.

Stages of breast cancer
There are different stages of breast cancer, defined according to various characteristics, such as the size of the tumor, whether the breast cancer cells are found within the initial tumor only (non-invasive breast cancer), or have started invading other tissues (invasive breast cancer). Furthermore, whether lymph nodes are involved and how far the cancer has spread beyond the breast. The earlier breast cancer is diagnosed, the more likely it can be treated successfully.

Treatment options for breast cancer
Treatment options for breast cancer depend on various factors including:

• The type of breast cancer
• The stage of breast cancer
• Hormonal factors
• How fast the breast cancer tumor is growing
• Age at diagnosis, general health, and menopausal status (whether a woman is still having menstrual periods)
  Whether the breast cancer is new (first diagnosis) or whether it is a recurring breast cancer
• Men can get breast cancer too
• Men can also develop breast cancer, however cases of male breast cancer are very rare. The deCODEme genetic test for breast cancer calculates genetic risk for female breast cancer only.
  

Chronic Lymphocytic Leukemia

A cancer of the blood and bone marrow
Chronic lymphocytic leukemia (CLL, also called chronic lymphoblastic leukemia) is a form of cancer affecting a subgroup of white blood cells called lymphocytes, which are produced in the bone marrow. Lymphocytes, along with other white blood cells, have a special role in protecting the body from infections caused by germs such as bacteria and viruses. They are programmed to divide and multiply when they come into contact with foreign antigens found on germs, and to help rid the body of the infectious agents.

CLL reduces the infection-fighting ability of blood
Normally, the bone marrow produces different types of blood cells, which are released into the blood stream as needed. When blood cells die, the bone marrow replaces them with new ones. This continuous cycle becomes disturbed in people who have CLL. The bone marrow starts producing abnormal lymphocyte cells that are unable to fight infections, but multiply in number. As these cancerous cells build up in the blood and bone marrow, often over long periods of time, the body has relatively fewer healthy lymphocytes. This reduces the overall ability of blood cells to fight infection. The proliferation of abnormal lymphocytes in the blood and bone marrow also affects other types of blood cells, causing symptoms such as anemia (due to fewer red blood cells) and an increased tendency for bleeding (due to fewer platelets).

CLL typically progresses at a slower rate than other leukemias
Symptoms of CLL can include anemia, fatigue, weight-loss, night-sweats, and enlarged lymph nodes. In many cases however, people with CLL can be symptom-free for years or even decades. A more serious and symptomatic disease develops if cancerous lymphocyte cells in the blood start invading other parts of the body, such as the lymph nodes, bone marrow, liver, or spleen.

Most commonly affects older adults
The average lifetime risk of getting CLL is about 0.5%, or 1 in 200. With an average age at diagnosis of around 70 years, CLL is mostly diagnosed in people over the age of 50, rarely in people under the age of 40, and is extremely rare in children. For unknown reasons, CLL is more often diagnosed in men than women.

Genetic variants found to increase risk of CLL
Six genetic variants, on chromosomes 2, 6, 11, 15 and 19, have been associated with increased risk of developing CLL. The deCODEme Complete Scan identifies these variants and provides an interpretation of the associated risk of CLL for individuals of European descent. At the current time, risk information for other ethnicities is not available for these variants.

Other risk factors
There are no proven controllable risk factors for CLL. The risk of developing this type of cancer does not seem to be affected by smoking, diet, exposure to radiation, or infections.

The main factors linked to an increased risk of developing CLL are:

• Age. The average age at diagnosis of CLL is around 70 years. It is rarely diagnosed in people under age 40, and is extremely rare in children.
• Gender. CLL is more common in males than females, although the reasons for this are not known.
• Race/Ethnicity. CLL is more common in North America and Europe than in Asia. Most experts think this reflects genetic differences between these groups rather than environmental factors as people maintain the same risk even when they move from one area to another.
• Family history. A person's risk of developing CLL may be higher than average when there is a family history of this disease or other blood and bone-marrow cancers. First-degree relatives of individuals with CLL have a two-to-four-fold increased risk of developing CLL.
• Exposure to certain chemicals is thought to increase risk of CLL, such as Agent Orange, an herbicide used by the U.S. military during the Vietnam War. Other studies have suggested that long-term exposure to certain other pesticides may also increase the risk of developing CLL. However, more research is needed to determine the impact of chemical agents on CLL risk.
• Early detection can delay symptom progression
• There are currently no recognized controllable risk factors for CLL. As there is no proven way to prevent this type of cancer, early detection provides physicians with the opportunity to monitor the disease progression closely and intervene appropriately as soon as symptoms develop.

Although CLL can be found on routine blood-tests (for example if a person's white blood cell count is unusually high), the American Cancer Society does not presently recommend routine screening for CLL.

Treatment options for people with CLL vary greatly, depending on the type of CLL, the disease stage, and whether or not the disease causes harmful symptoms. In symptom-free patients, treatment may not be necessary.

As CLL can be a symptom-free disease for a long time and treatment may cause side effects, doctors often advise watchful waiting upon initial diagnosis. Watchful waiting does not reduce the effectiveness of future treatment should it become necessary.

Colorectal Cancer

A common cancer among men and women
Colorectal cancer is the fourth most common cancer in males and females in the Unites States and worldwide, and it is the second leading cause of cancer death in the US. The average risk that an individual in the US will develop colorectal cancer in their lifetime is 6%.

Up to 30% of cases may be due to genetic factors
Individuals with a first-degree relative (sibling, parent, or child) with colorectal cancer are twice as likely to develop the disease as the general population. The risk is greater if a relative is diagnosed at an early age (younger than 60 years) or if more than one relative has been diagnosed with the disease. It has been estimated that up to 30% of colorectal cancers may be due to genetic factors.

A fraction of cases are due to rare genetic mutations
A fraction (~5%) of colorectal cancer cases occur in families with multiple cases of the disease. An example of such a condition is multiple polyposis of the colon, where the inner surface of the colon is covered with thousands of polyps. In some instances, these cases are known to be caused by specific mutations in genes that substantially increase the risk of the disease. Individuals belonging to such families should seek counselling about preventive measures.

Please note that the deCODEme genetic scans do not identify such rare and highly familial cancer genes, including APC, MLH1, MSH2, MSH6, and PMS2.

Common genetic variants are associated with colorectal cancer
To date, eight common genetic variants have been found that increase the risk of developing colorectal cancer. Two variants are located on chromosome 8 (one in the EIF3H gene and the other close to POU5F1P1) and then one variant on each of chromosomes 10, 11, 14 (close to the BMP4 gene), 15 (in the CRAC1 gene), 18 (in the SMAD7 gene) and 20.

deCODEme can calculate your genetic risk for colorectal cancer for the common variants
The deCODEme Complete Scan identifies the eight variants listed above and provides interpretation of the associated risk of developing colorectal cancer in individuals of European descent. For individuals of East Asian origin, the deCODEme Complete Scan provides interpretation of colorectal cancer risk associated with two variants; on chromosome 8 (close to POU5F1P1) and a variant in the SMAD7 gene on chromosome 18. At the present time data is not available to support risk asessments for individuals of other ethnicities for the variants listed above.

Risk factors
Some people are more likely to develop colorectal cancer than others. The major risk factors are:

• Age: More than 90 percent of patients are diagnosed over the age of 50.
• Polyps: Colorectal tumors often arise from polyps in the colon. Such polyps are common in people over 50 but only some polyps will become cancerous.
• Chronic inflammatory diseases of the bowel: Individuals with ulcerative colitis or Crohn’s disease have an increased risk of developing colorectal cancer.
• Diet and lifestyle: Some studies suggest that high-fat diets with low levels of fiber, calcium, and folate may increase the risk of colorectal cancer. It has also been suggested that people with diets poor in fruit and vegetables, those who smoke, and those who are obese may have an increased risk of the disease.
• Genetics: Individuals with a first-degree relative (sibling, parent, or child) with colorectal cancer are twice as likely to develop the disease as the general population. The risk is greater if a relative is diagnosed at an early age (younger than 60 years) or if more than one relative has been diagnosed with the disease. It has been estimated that up to 30% of colorectal cancers may be due to genetic factors.
  

Some risk factors can be avoided
Some risk factors for developing colorectal cancer can be avoided, others cannot. Avoiding the controllable risk factors, like smoking, and maintaining a regular exercise program and a healthy diet may prevent or delay the development of some types of cancer.

Screening guidelines for colorectal cancer
If abnormal tissue, polyps, or colorectal cancer are caught early, there is a higher chance of preventing development of disease or curing the disease while it is in its early stages. For this reason, the American Cancer Society recommends that, beginning at age 50, all individuals should follow 1 of 5 testing schedules:

• Yearly fecal occult blood test (FOBT) or fecal immunochemical test (FIT).
• Flexible sigmoidoscopy every 5 years.
• Yearly FOBT or FIT, plus flexible sigmoidoscopy every 5 years.
• Double-contrast barium enema every 5 years.
• Colonoscopy every 10 years.
  

Positive tests should be followed-up with a colonoscopy. Furthermore, people who have been diagnosed with inflammatory bowel disease or have a strong family history of colorectal cancer should talk to their doctor about starting colorectal cancer screening earlier and/or undergoing screening more often. The prognosis is strongly associated with how advanced the disease is at diagnosis; if the cancer is caught early, cure rates are high. Therefore, colorectal cancer screening presents an opportunity for early cancer detection and cancer prevention.

Lung Cancer

Lung cancer is the primary cause of cancer death
In the United States, lung cancer is the primary cause of cancer death among both men and women, killing over 160 thousand people in 2007, which exceeds the combined mortality attributable to breast, prostate and colon cancer. In 2007 there were more than 200 thousand new cases of lung cancer diagnosed in the United States: more among men than women. On average, 1 in 13 men and 1 in 16 women will be diagnosed with lung cancer (a lifetime risk of 8% and 6%, respectively).

Smoking is the single most important risk factor for lung cancer
The single most important factor influencing the risk of developing lung cancer is smoking. In the United States, smoking is estimated to account for 87% of lung cancer cases (90% in men and 85% in women). The lifetime risk of developing lung cancer is 17.2% among male smokers and 11.6% among female smokers. This risk is significantly lower in non-smokers: 1.3% in men and 1.4% in women.

Genetic factors also contribute to risk of developing lung cancer
Epidemiological studies have shown that genetic factors also contribute to the risk of developing lung cancer. Recently, scientists at deCODE Genetics discovered an association between the diagnosis of Lung cancer and two specific variants in the genome. One variant is located on chromosome 15 within the nicotinic acetylcholine receptor gene cluster. In smokers, this same variant also increases the risk for Nicotine Dependence and Peripheral Arterial Disease. The second variant is located on chromosome 5 near the TERT gene.

deCODEme can calculate your genetic risk for lung cancer
The deCODEme Complete Scan and the deCODEme Cancer Scan identify the two risk variants and provide an interpretation of the associated risk for developing lung cancer for individuals of European descent who smoke. More studies need to be conducted to test if the variant also increases risk of lung cancer in people who do not smoke. Currently no risk data are available for people of other ethnicities for these variants.

• Risk factors for lung cancer
  Smoking is the greatest known risk factor for lung cancer and is estimated to be responsible for approximately 90% of lung cancer in men and 85% in women. Lung cancer risk attributable to tobacco smoking is strongly affected by the duration of smoking, and declines with increasing time from cessation. Thus, the estimated lifetime risk of lung cancer among former smokers ranges from approximately 6% in smokers who give up at the age of 50, to 10% for smokers who give up at age 60, compared to 15% for lifelong smokers and approximately 1% in never-smokers.
  Secondary smoke is estimated to cause approximately 3,000 lung cancer deaths per year among non-smokers and contributes to more than 35,000 deaths linked to cardiovascular disease.
• Genetics. Regardless of exposure to tobacco smoke, there are important individual differences in the risk of developing lung cancer, some of which are attributable to genetic factors. Thus, for example, even though smoking is the primary cause of lung cancer, only about 15% of lifelong smokers will actually develop this disease. Genetic factors may influence who ends up developing the disease. The role of genetics is further demonstrated by the fact that close relatives of lung cancer patients have an approximately two-fold greater risk of developing the disease compared to the general population.
• Environmental pollutants. Exposure to a variety of environmental factors or industrial substances has been associated with increased risk of lung cancer. These include asbestos, radon and arsenic. Certain lung diseases can also increase the risk for lung cancer. However, these factors combined still contribute much less to the disease risk than tobacco smoking.
  

The best way to prevent lung cancer is not to smoke
The best way to avoid lung cancer by far is not to smoke and to avoid second-hand smoke and other environmental factors that may increase the risk of the disease.

Dietary choices may affect lung cancer
There is some evidence that suggests that a diet rich in fruit may have protective effect against lung cancer. Furthermore, smokers may benefit from eating vegetables. Several large studies have been conducted in order to test if intake of vitamins or other supplements might protect against lung cancer. To date, there is limited evidence that this might be the case. Highly publicized studies of beta-carotene and vitamin A supplementation in smokers actually showed an increase in lung cancers in the supplementation groups. In another study of over 75,000 individuals it was shown that the long-term use of supplemental multivitamins, such as vitamin C, vitamin E, and folate did not reduce the risk of lung cancer. On the contrary, the results of the study indicated that high doses of vitamin E might even increase the risk of lung cancer.

Lung cancer screening
Individuals who are identified as being at high risk for lung cancer may be referred to have chest X-rays or sputum cytology examination. In addition, a spiral CT scan is a newly-developed procedure for lung cancer screening. Numerous lung cancer screening trials are currently taking place but presently, the U.S. Preventive Services Task Force (USPSTF) concludes that evidence is insufficient to recommend for or against screening asymptomatic persons for lung cancer.

Treatment options for lung cancer
The outcome of lung cancer depends on the tumor type, how advanced the disease is when it is diagnosed, and the general health of the person diagnosed. Overall, lung cancer is one of the most difficult cancers to treat. If the disease is diagnosed early, then more treatment options are available and prognosis is better. Treatment options include surgery, radiation, chemotherapy, or a combination of these.

Prostate Cancer

The prostate is part of the male reproductive system
The prostate is a small gland, normally about the size of a walnut, located under the urine bladder. The prostate is part of the male reproductive system; it makes part of the seminal fluid needed to carry sperm out of the man’s body. The urethra, the narrow tube that runs the length of the penis and carries both urine and semen out of the body, runs directly through the prostate. This is why the first signs of prostate enlargement are often related to urinary problems.

Prostate cancer is typically a slow growing cancer
Prostate growths can be benign (not cancer) or malignant (cancer). Prostate cancer occurs when cells within the prostate start to multiply uncontrollably. In most cases, prostate cancer is a relatively slow-growing cancer, which means that it takes a number of years to become detectable. A small percentage of prostate cancers however, grow more rapidly. Unfortunately, it is difficult to predict which prostate cancers will grow slowly and which will grow more aggressively.

If detected early, prostate cancer is highly curable
In early stages of prostate cancer, while the tumors are enclosed within the prostate, the disease is often curable with cure rates of 90% or more. Unfortunately, at this highly curable stage, prostate cancer produces few or no symptoms and can be difficult to detect. In general, the earlier the prostate cancer is caught, the more likely it is that treatment will be successful.

Prostate cancer is the most common non-skin cancer among men
During their lifetimes, 1 in 6 men will be diagnosed with prostate cancer (lifetime risk of 16%), and 1 in 33 men will die of the disease (3% lifetime risk). Over 200,000 new cases of prostate cancer will be diagnosed, and prostate cancer will lead to approximately 27,000 deaths in the US this year. A man is over 30% more likely to be diagnosed with prostate cancer in his lifetime than a woman is to be diagnosed with breast cancer in hers.

Genetics contribute significantly to prostate cancer risk
Genetic variants are a significant contributor to the risk of developing prostate cancer. In fact, of all cancer types, prostate cancer is most closely linked to genetic risk factors. There are thirteen genetic variants that are known to increase the risk of developing prostate cancer: three in the chromosome 8q24 region, two on chromosome 17q (one of which is located within the TCF2 gene) and one on each of the following chromosomes: 2, 3, 5, 6, 7, 10, 11 and X.

deCODEme can calculate your genetic risk for prostate cancer
The deCODEme Complete Scan and the deCODEme Cancer Scan identify all thirteen variants listed above and provide interpretation of their associated risk for developing prostate cancer in customers of European descent. In African-Americans, the deCODEme scans currently provide risk assessments for two out of the three variants on chromosome 8q24. Currently risk data are not available for people of other ethnicities for the variants listed above.

Risk factors for prostate cancer

• Age: Prostate cancer is rare in men younger than 45 years, with 65% of cases diagnosed in men over the age of 65.
• Ethnicity: African American men are 1.6 times more likely to develop prostate cancer than men of northern European descent and are nearly 2.5 times more likely to die from the disease.
• Genetics: Men with a single relative with prostate cancer are twice as likely to develop prostate cancer, while those with two or more relatives are nearly four times as likely to be diagnosed with the disease. The risk is even higher if the affected family members were diagnosed before the age of 65.
  

Prevention and treatment
Early diagnosis is the key to beating prostate cancer. When diagnosed and treated early, over 90% of prostate cancer cases can be cured. Current guidelines from the American Cancer Society suggest that all men 50 years and older without known risk factors should be screened every other year for prostate cancer with a blood test and a rectal exam. Men with risk factors for prostate cancer, such as a family history or African American ethnicity, should start screening earlier, by age 40 or 45. Realizing one’s risk of prostate cancer, including genetic risk, is the first step in making an informed decision about when to seek medical advice and start screening for prostate cancer.

Thyroid Cancer

The thyroid produces metabolism-regulating hormones
The thyroid gland is a butterfly-shaped gland located in the lower front of the neck, below the larynx (‘Adam’s apple’), that is part of the body´s hormone-producing endocrine system. The hormones produced by the thyroid gland help regulate metabolism, that is the rate at which the body burns energy. A thyroid gland that is not active enough in producing hormones can slow metabolism, resulting in weight-gain, fatigue, and increased sensitivity to cold temperatures. Too much hormone-production can lead to increased metabolism, resulting in weight-loss, increased heart rate and sensitivity to heat.

Thyroid cancer is the most common endocrine cancer
Thyroid cancer is the most common cancer of the endocrine system, its incidence in industrialized countries has been rising over the past few decades. In 2008, the estimated number of new cases in the U.S. was about 37,000 with a gender bias of about three females affected for each male. The average age at diagnosis is around 60 years for males and 47 years for females.

High cure-rate if diagnosed early
There are four main types of thyroid cancer. Those referred to as papillary and follicular types, account for over 90% of all thyroid cancers, while the rarer medullary and anaplastic types account for the remaining 10%. In general, thyroid cancer is one of the least deadly cancers. If diagnosed at an early stage, treatment is usually very effective and survival prospects are good.

Thyroid cancer has a strong genetic component
As is the case with most cancers, thyroid cancer is thought to be the result of both environmental and genetic factors. However, thyroid cancer has been estimated to have one of the strongest genetic components of all cancers, although to date, very few genetic variants have been discovered.

Common genetic variants contribute to an increased risk
Scientists at deCODE genetics have identified two genetic variants, on chromosomes 9 and 14, associated with increased risk of thyroid cancer. The variants contribute to an increased risk of the two main types of thyroid cancer, papillary and follicular. Furthermore, the risk alleles are associated with younger age at diagnosis.

deCODEme can calculate your genetic risk for thyroid cancer
The deCODEme Complete Scan and the deCODEme Cancer Scan identify these variants and provide an interpretation of the associated risk for the development of thyroid cancer for individuals of European descent. At this time risk information is not available for other ethnicities.

Known risk factors for thyroid cancer
There is still much to learn about the causes of thyroid cancer, however the following factors are known to contribute to and individual´s risk:

• Radiation exposure, including radiation in the form of repeated X-rays of the neck.
• Family history risk has been reported to be highest for first degree male relatives of male patients but lowest for first degree female relatives of female patients.
• Gender and age. For reasons that aren’t clear, women are two to three times more likely to develop thyroid cancer than men. Although thyroid cancers can occur in people of all ages, most cases of papillary and follicular thyroid cancer are found in people between the ages of 20 and 60 years.
• Ethnicity. Individuals of European, Asian and Pacific Islander ancestry are more likely to develop thyroid cancer than African Americans, American Indians or Hispanics.
• Certain inherited conditions for example familial adenomatous polyposis can increase the risk of papillary thyroid cancer.
• Iodine is an element found in seafood, some vegatables and in iodized salt, and has been identified by some studies as a possible risk factor for thyroid cancer. Follicular thyroid cancers are more common in areas of the world where people’s diets are low in iodine. This risk factor does not play a significant role where dietary iodine is plentiful. More studies are needed to determine the role of iodine a risk factor for thyroid cancer.
  

Knowing your genetic risk is important for prevention
Since thyroid cancer seems to have such a strong genetic basis, knowing your genetic risk and monitoring possible symptoms of thyroid cancer can be preventative initself.

Avoiding radiation exposure is of course is always recommended, although current X-ray technology is such that the benefits almost always outweigh the risk.

Early thyroid cancer can have no apparent symptoms, or it can have symptoms associated with changes in thyroid hormone production (i.e. weight-loss or weight-gain, fatigue, change in heart-rate and heat sensitivity etc). Some patients with thyroid cancer become aware of a gradually enlarging lump in the front portion of the neck which usually moves with swallowing. Occasionally, the lump may cause a feeling of pressure, hoarseness or change of voice or trouble breathing or swallowing.

There are many reasons the thyroid gland might be larger than usual, and most of the time it is not cancer. Those who find an unusual lump in their neck should always bring this to the attention of their physician, even in the absence of other symptoms.

Fortunately, most types of thyroid cancer can be diagnosed early and cured completely. Treatment usually entails removing the suspected part of the thyroid gland and any abnormal lymph glands. If cancer is confirmed, radioactive iodine treatment is usually recommended in order to destroy any remaining malignant thyroid cells and to reduce the risk of cancer recurrence.

ABO Blood Types

All human blood is similar, but some blood types are more similar than others
In most respects all humans have very similar blood. As a result, it is possible to transfer blood from one human to another. This procedure, called blood transfusion, is now routine and safe in modern medical practice, and has saved the lives of countless people since being widely adopted in the 1940s. However, you cannot receive blood from just anyone. Your blood must be compatible with that of the blood donor.

ABO blood types are determined by red blood cell antigens
There are four different ABO blood types, named A, B, O and AB. Your ABO blood type depends on which kind of glycoprotein or antigen is found on the outside of your blood cells. These glycoproteins come in three forms and are referred to as A, B and O.

The gene that determines your ABO blood type is found on chromosome nine
The gene that determines your ABO blood type is found on chromosome 9 and is called ABO glycosyltransferase. In the simplest terms, this gene may be said to come in three different forms, that is, it has three different alleles. These alleles are also named A, B and O, because each is responsible for the production of its namesake glycoprotein (antigen). It is therefore the combination of alleles that you inherited from your parents that determines which glycoproteins (antigens) are found on your blood cells and thereby your ABO blood type.

Six possible allele combinations determine four distinct ABO blood types
The six possible distinct combinations of alleles (and antigens), and the four distinct blood types they determine, are shown below:

Combination of ABO alleles ABO antigens on the surface of blood cells ABO blood type
1. AA A A
2. AO A and O
3. BB B B
4. BO B and O
5. AB A and B AB
6. OO O O

The deCODEme Complete Scan identifies which combination of the three ABO alleles you carry on chromosome 9 and therefore which blood type you are likely to have. At the present time, sufficient predictive data is only available for customers of European ancestry.

Please note that the results of the deCODEme scan cannot replace a traditional ABO blood typing test that is used for critical medical procedures such as blood transfusion or organ transplantation. What we provide here is a prediction of your ABO blood type based on the genetic variants included in the deCODEme Complete Scan.

Hemochromatosis

In hereditary hemochromatosis (HH) more iron is absorbed than is needed. With the exception of menstruation in women, the human body has no natural means of getting rid of extra iron. As a result, iron builds up in individuals with HH and is deposited throughout the body. Over time iron can reach toxic levels in tissues, causing dysfunction and failure in major organs such as the liver, pancreas, heart, thyroid, pituitary gland, and joints.

Hereditary hemochromatosis can have a variety of symptoms, ranging from mild conditions like fatigue, weakness, abdominal and joint pain to more severe ones associated with failures in the aforementioned organs. Undiagnosed and untreated, HH can have serious consequences over time, including increased risk for liver diseases, heart problems, arthritis, depression, impotence, infertility, hypothyroidism, pituitary hormone deficiency, diabetes and even some forms of cancer.

The worldwide prevalence of HH in 18-70 year old individuals is estimated to range from 1.5 to 3 per 1000 individuals, it affects about one million individuals in the US. However, the disease is thought to be significantly under-diagnosed and is more common in men than in women. The prevalence of HH also varies considerably between populations, being most common in individuals of European descent.

Hereditary hemochromatosis actually has a geographic distribution that is thought to reflect the historical movements of people of northwestern Europe. It is most frequent in populations surrounding the North Sea; Norway, Denmark, Iceland, Germany (west and south), France, the United Kingdom, and Ireland. It is less frequent in southern Europe, and almost non-existant in Africa. In the United States, the frequency in individuals of European descent is similar to that seen in northern Europe. The highest frequency of the disease is found in the Irish population. This and the geographic distribution of the disease, has led scientists to believe that hemochromatosis is the result of a relatively recent mutation originating in a Celtic population (indeed, HH is sometimes referred to as the “Celtic curse”). Some scientists have however proposed that the mutation is of Viking or Germanic origin.

Hereditary hemochromatosis is caused by mutations in the HFE gene on chromosome 6. There are more than 20 known mutations in the HFE gene, but the most important for HH identified to date are two sequence variants, C282Y and H63D. The C282Y mutation explains 80 to 90 percent of all diagnosed cases of HH in populations of northwestern European ancestry.

The deCODEme Complete Scan identifies the C282Y and H63D sequence variants in the HFE gene on chromosome 6 and gives an interpretation of the associated genetic risk for hereditary hemochromatosis.

risk factors
The main risk factors associated with hereditary hemochromatosis are:

• Genetics: Hereditary hemochromatosis shows an autosomal recessive pattern of inheritance. This means that an individual with the disease must have inherited a mutated and non-functional copy of the HFE gene from both parents. Such an individual is said to be homozygous for mutated copies of the HFE gene. In populations of northern European descent, one in 200-250 are homozygous (have two mutated copies) for C282Y. One in 50 are compound heterozygotes (have one C282Y mutation and one H63D mutation). One in 8-10 are heterozygotes for C282Y (carriers of the mutation). Although two copies of the mutated HFE gene are required to have the disease, not everyone who has two copies actually gets the disorder, meaning in genetic terms, that the genetic variants do not have full penetrance . Most studies report that 60-95% of C282Y homozygotes show symptoms of the disease.
• Ancestry: Hereditary hemochromatosis is found almost exclusively in individuals of northern European ancestry.
• Age: Older people are more likely to develop the disease than younger people. Symptoms do not usually appear in men until after the age of 40. In women, symptoms usually do not appear until after the age of 50 (i.e. after menopause). Individuals carrying two mutated and non-functional copies of the HFE gene rarely develop HH as young children.
• Other factors: The severity of the disorder varies between individuals homozygous for mutated HFE gene copies. Some people may never have symptoms or complications of the disorder while others can be severely affected. Certain factors, including both lifestyle and genetic factors, seem to affect the symptoms and progress of the disorder for those who have inherited mutated copies of the gene:
  Other genes, besides the hemochromatosis gene, may modify the severity of the disease,
  Vitamin C in the diet can increase the amount of iron the body absorbs from food and make hemochromatosis worse,
  Alcohol use can increase the risk of liver damage and cirrhosis,
  Certain other conditions, such as hepatitis (inflammation of the liver), can increase the effects of iron overload on damage to the liver.
  

prevention
The key to preventing hemochromatosis is early diagnosis and treatment. Diagnosis of HH is typically based on blood tests that measure transferrin, iron saturation and serum ferritin concentration, but also on molecular genetic testing for the C282Y and H63D mutations in the HFE gene.

Due to incomplete penetrance, the genotype provided by the deCODEme Genetic Scan is in itself insufficient for the diagnosis of HH, but should be considered as evidence of susceptibility to developing the disease. Individuals identified as C282Y homozygotes or C282Y/H63D compound heterozygotes should undergo further testing to identify or exclude iron overload.

As previously described, not everyone who inherits the hemochromatosis mutations develops the disease. For those who have confirmed iron overload, physicians may recommend preventive measures such as dietary changes aimed at reducing iron absorption, for example avoiding taking in extra iron (for example in multivitamins), limiting intake of vitamin C (as it increases iron absorption) and limiting alcohol intake to reduce risk of liver disease.

In terms of treatment, HH is actually one of the few genetic disorders for which there is a relatively simple and effective therapy; iron levels are lowered simply by removing blood (a procedure called phlebotomy).

When phlebotomy is started early in the course of the illness, it can prevent most of the complications associated with the disease. However, even if phlebotomy is started after complications have occurred, the treatment can still decrease symptoms and improve life expectancy.

Venous Thromoembolism

Deep vein thromboses most often occur in leg veins
When a blood clot (thrombus) forms inside a person´s vein, he or she is said to suffer from venous thrombosis. If the vein affected by a blood clot is deep inside the body, rather than close to the surface of the body, the condition is referred to as deep vein thrombosis (DVT) and most often occurs in the veins of the legs or pelvis.

Venous blood clots can break off and lodge in the lungs
Patients with DVT are in danger of suffering a pulmonary embolism, which occurs when a venous blood clot breaks off (completely or partially), travels with the bloodstream and lodges in one of lung’s narrow arteries. The resulting blockage of blood flow can cause permanent damage to the affected lung, heart failure and death.

DVT can go undetected until it causes pulmonary embolism
Individuals who suffer from either DVT or pulmonary embolism are collectively diagnosed as having venous thromboembolism (VTE). Each year, one out of 1000 individuals of European ancestry in the United States is diagnosed for the first time with VTE. About one-third of people with this condition experience a pulmonary embolism and one-third develops VTE again within ten years of the initial diagnosis. The proportion of people with VTE is likely to be underestimated as it is well recognized that a number of cases remain undiagnosed.

A number of genetic factors contribute to the risk of VTE
It is believed that a number of genetic factors contribute to the development of VTE. One of these is Factor V Leiden, a mutation in the Factor V gene on chromosome 1 that results in thrombophilia, or an increased tendency to form abnormal blood clots in blood vessels. Individuals with this mutation have a three to four-fold increased risk of developing VTE in their lifetime. The Factor V Leiden variant is quite common in populations of European ancestry, but less common in other ethnicity groups.

deCODEme can calculate your genetic risk
The deCODEme Complete Scan and the deCODEme Cardio Scan identify the Factor V Leiden variant in the Factor V gene and provide interpretation of the associated risk of developing VTE for individuals of European ancestry. Currently, information about the risk of VTE conferred by this variant is not available for individuals of other ethnicities.

Risk factors

• Age and gender. Age is a strong risk factor for development of venous thromboembolism (VTE) with a dramatic increase after age 60. Recurrent VTE is more common in men than women.
• Surgeries. Major surgery, as well as trauma and fractures, are known to increase the risk of VTE.
• Chronic illnesses. Increased risk of VTE accompanies various chronic illnesses such as cancer, stroke and congestive heart failure. A previous diagnosis of VTE is a risk factor for further episodes.
• Immobility Immobility due to surgery, trauma, and chronic illness is associated with VTE as described above. Prolonged bed rest and long journeys by airplane or car, even in otherwise assumed healthy individuals, also increase the risk of VTE.
• Other conditions that have been associated with greater risk of VTE include pregnancy, the postpartum period, varicose veins, obesity, estrogen treatment and the antiphospholipid antibody syndrome.
• Ethnicity. In the United States the incidence of VTE has been found to be highest in African-Americans followed by individuals of European descent. The risk for Hispanics is about half that of populations of European origin while Asians are at a markedly lower risk.
• Genetics. An inherited risk factor can be identified in over half of patients with deep venous thrombosis without identifiable cause or thrombosis at a young age. Factor V Leiden, is detected in about 5% of individuals of European origin, but is rare in other ethnic groups. The reported frequency in Hispanics is around 2%, 1% in African-Americans and 0.5% or less in Asians.
  

Prevention and treatment
Avoiding long periods of immobility helps prevent the formation of deep vein thrombosis. Once a blood clot has developed in a deep vein, the treatment goals include preventing enlargement of the blood clot, preventing a pulmonary embolism and preventing recurrences of venous thrombosis.

The mainstay of therapy is anticoagulation (thinning of the blood) with duration of treatment depending on number of episodes and the presence or absence of blood clots in the lungs. Occasionally a permanent metal filter is placed in the largest vein below the heart (the inferior vena cava) to prevent large blood clots from reaching the arteries of the lung.

Warfarin Metabolism

Warfarin is a ‘blood-thinning’ medication
Warfarin is a type of medication commonly known as a blood thinner or anticoagulant. It is widely used to decrease the risk of blood clot formation in arteries and veins and to prevent existing blood clots from growing and breaking off. The primary danger from blood clots is when they get lodged in narrow arteries, for example in the brain (causing stroke) or in the lungs (causing pulmonary embolism).

Physicians must monitor patients closely when starting warfarin therapy
Determining the appropriate dose for someone starting warfarin therapy is extremely challenging, since the dose required for recommended therapeutic levels differs between individuals. A physician prescribing warfarin must monitor its blood-thinning effect by frequent blood-testing, using the International Normalized Ratio (INR) test. On the basis of results from such tests, the physician must adjust the dose of warfarin to ensure the desired therapeutic level of blood thinning.

Bleeding can occur if the dose exceeds an individual’s requirements
The most common adverse side-effect of warfarin therapy is internal bleeding. The risk of major bleeding is low, but must always be taken into consideration when therapy with warfarin is initiated. The risk of bleeding due to warfarin can increase when the dose exceeds an individual’s requirements and due to interaction with other medications or certain foods.

Environmental and genetic factors affect warfarin dose requirements
Many factors affect the warfarin dose requirements of individuals, including age, weight, diet, disease history and other medications. In addition, it is now known that genetic variants in the genes encoding vitamin K epoxide reductase (VKORC1) and cytochrome p450 2C9 (CYP2C9) have a significant impact on people’s sensitivity to warfarin. Individuals with particular variations in these genes require a lower warfarin dose to maintain therapeutic levels of anticoagulation. Individuals with other variations require higher doses. Together these genetic variations explain about 50% of the required dose difference between individuals and therefore constitute important information for physicians when initiating warfarin therapy.

deCODEme interprets the genetics of your warfarin metabolism
The deCODEme Complete Scan identifies the rs9923231 sequence variant in the VKORC1 gene on chromosome 16 and the CYP2C9*1, CYP2C9*2 and CYP2C9*3 variants in the cytochrome p450 2C gene on chromosome 10 and provides an interpretation of the associated impact on warfarin sensitivity for individuals of European descent.

Please note that these variants only provide information about your genetic propensity in relation to warfarin sensitivity and that many other factors can affect your actual sensitivity to warfarin. It is essential that any decisions about warfarin therapy and dose size be taken in consultation with a physician.

Factors associated with warfarin sensitivity
Both genetic and environmental factors such as foods and medications can affect the anticoagulation effect of warfarin:

• Genetics. Variants in both vitamin K epoxide reductase (VKORC1) and cytochrome p450 2C9 (CYP2C9) have a significant impact on warfarin sensitivity. Carriers of specific variations may be more sensitive to warfarin and may therefore require significantly lower doses than those with other variations. Variations in VKORC1 have a much greater impact on warfarin sensitivity than variations in CYP2C9, particularly during the initiation of therapy.
• Ethnicity. There are significant differences in warfarin dose requirements among different ethnic groups. Specifically, it has been recognized that people of East Asian descent require on average a 30-40% lower warfarin dose than individuals of European descent. In recent years it has become apparent that the VKORC1 gene variants that are associated with lower warfarin doses are much more common in Asians than Europeans, explaining most, if not all, of the difference attributable to ancestry.
• Foods high in vitamin K. Vitamin K is a natural blood-clotting factor and can reverse the blood-thinning effects of warfarin. Broccoli, lettuce, spinach and liver are all high in vitamin K. It is not recommended to eliminate these foods from the diet when taking warfarin, but to eat them in consistent amounts so as to maintain a balance with respect to warfarin dosing.
• Alcohol. Excessive use of alcohol is also known to affect the metabolism of warfarin and can increase its blood-thinning effects.
• Interaction with other medications. Many medications interact with warfarin, affecting its anticoagulation activity, including aspirin, some antibiotics and birth control pills. Warfarin also interacts with many herbal remedies.
  

Bones, joints and muscles:

Gout

Uric acid is produced by the body when it breaks down purines, substances that are found naturally in the body and in food. Purines are particularly rich in certain foods, such as liver, anchovies, herring, asparagus and mushrooms. Normally, uric acid dissolves in the blood and passes through the kidneys into the urine. However, when the body either produces too much uric acid or the kidneys excrete too little uric acid, it can build up, forming sharp, needle-like urate crystals in joints or surrounding tissues that cause sudden inflammation, pain, swelling and stiffness in the affected joint, a condition referred to as gout. However, people with elevated levels of uric acid in their blood do not always develop gout and conversely, not everyone that experiences repeated attacks of gout have elevated levels of uric acid.

Gout usually attacks the big toe (approximately 75% of first attacks), but it can also affect other joints such as the ankle, heel, instep, knee, wrist, elbow, fingers, and spine. Untreated and chronic gout can lead to deposits of hard lumps of uric acid (tophi lumps) in and around joints, kidney stones and decreased kidney function.

Approximately one million people in the United States suffer from attacks of gout. Gout is about nine times more common in men than in women. Among the male population in the United States, approximately 10% have hyperuricemia.

Two genetic variants have been found to be associated with gout. The first variant is in the GLUT9/SLC2A9 gene and the second is in the ABCG2 gene.

The deCODEme Complete Scan identifies these variants and provides an interpretation of the associated risk for the development of gout for individuals of European descent.

Risk Factors
Although an elevated blood level of uric acid (hyperuricemia) is associated with an increased risk of gout, the relationship between hyperuricemia and gout is not fully understood. Risk factors for hyperuricemia and/or gout include the following:

• Age and gender: Gout is nine times more common in men than in women, primarily because men tend to have higher levels of uric acid in their blood than women. The disease predominantly attacks males after puberty and is most common in males between 40 and 50 years of age. Women become increasingly susceptible to gout after menopause.
• Ethnicity: In the United States, gout is twice as prevalent in African American males as it is in males of European descent.
• Genetics: If members of your family have had gout, then you are more likely to develop the disease. Twenty percent of people with gout have a family history of the disease.
• Diet: High levels of uric acid in the blood are mostly caused by protein rich foods. Alcohol intake can cause acute attacks of gout. Gout is more common in affluent societies due to a diet rich in proteins, fat, and alcohol.
• Medication: The use of thiazide diuretics, which are commonly used to treat hypertension, and low-dose aspirin can increase uric acid levels. So can the use of anti-rejection drugs prescribed for people who have undergone an organ transplant.
• Other diseases: Typically, persons with gout are obese, predisposed to diabetes and hypertension, and at higher risk of heart disease.
  
  

Prevention and Treatment
Prevention of hyperuricemia and acute gout involves maintaining adequate fluid intake, weight reduction, dietary changes, reduction in alcohol consumption, and use of medication to reduce hyperuricemia:

• Dietary changes: Reducing the amount of animal protein in your diet is important, because high-protein foods increase the blood level of uric acid. Organ meats (liver, brains, kidney and sweetbreads), anchovies, herring and mackerel are particularly high in purines, a substance which the body breaks down into uric acid.
• Reduce alcohol consumption: Alcohol can inhibit the excretion of uric acid via the kidneys and hence cause an acute attack of gout. When suffering a gout attack, it is best to avoid alcohol completely.
• Fluids: Adequate fluid intake is particularly important as fluids help dilute uric acid in blood and urine.
  Weight reduction: If overweight, weight loss can be helpful in lowering the risk of recurrent attacks of gout.
• Medication: Medication can be prescribed to lower blood levels of uric acid. These medications either decrease uric acid blood levels by increasing the excretion of uric acid into the urine (such as probenecid and sulfinpyrazone), or lower the blood uric acid level by preventing uric acid production (such as allopurinol).
  

Treatment for acute gout usually involves medication, prescribed according to health status and previous medical history. These can include Nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine or steroid medications such as prednisone. Elevating the inflamed joint and applying ice packs can be helpful to reduce pain and decrease inflammation. Patients should avoid medication containing aspirin, when possible, because aspirin prevents kidney excretion of uric acid.

Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease of the joints. It is a progressive disease that can lead to long-term joint damage, resulting in chronic pain, loss of function, and disability.

RA is also a systemic disease, which means it can affect other organs in the body including the skin, heart, lungs, eyes, and muscles.

RA is thought to affect approximately 2.1 million Americans, or 1% of the US population. In Asia the prevalence is similar. About 60% of RA patients are unable to work 10 years after the onset of disease. RA can affect anyone, including children, but 70% of people with RA are women. Onset usually occurs between 30 and 50 years of age.

Genetic variants are known to increase the risk of developing Rheumatoid arthritis; a variant in or near the HLA-DRB1 gene on chromosome 6p, the PTPN22 gene on chromosome 1, the STAT4 gene on chromosome 2, the IL23 gene on chromosome 4, the TRAF1-C5 gene on chromosome 9, the OLIG3-TNFAIP3 gene region on chromosome 6q and in the PADI4 gene on chromosome 1. Of these the HLA-DRB gene contributes by far the strongest effect to the risk of developing Rheumatoid arthritis. The PADI4 gene contributes to the risk of RA in East Asians but not people of European descent.

The deCODEme Complete Scan identifies variants in six out of the seven genes listed above and provides interpretation of their associated risk for the development of RA in customers of northern European descent. In East Asians, the deCODEme Complete Scan currently provides risk assessments for two out of the seven variants; the STAT4 and PADI4 genes. Currently no data are available for people of other ethnicities for the variants listed above.

risk factors
Gender and genetic factors are the most common known risk factors for RA. In addition, there are certain environmental factors that increase the risk of developing RA, including cigarette smoking and high body mass index (BMI).

• Gender: Women develop RA two to three times more often than men and their RA symptoms typically improve during pregnancy. Women develop RA more often than expected in the year after pregnancy and symptoms can increase after the baby is born. While women are two to three times more likely to get RA than men, men tend to be more severely affected by the disease.
• Genetics: Family history of RA is a known risk factor and studies have shown that genes contribute to the risk of RA. There is an increased risk among siblings of RA patients as well as among more distantly related individuals (cousins).
  prevention and treatment
  

There is no known way to prevent RA other than a healthy lifestyle, which seems to reduce the risk of developing the disease. Healthy diet, regular exercise, and maintaining an ideal weight are highly recommended. Smoking has been shown to increase the risk of developing RA. If you are a smoker, the increased risk of developing RA gives you another reason to quit.

While currently there is no effective cure, RA can be controlled through the use of new drugs, exercise, joint protection techniques, and self-management techniques. The goal of treatment is to relieve pain, reduce inflammation, stop or slow joint damage, improve general functioning, and improve the sense of well-being.

Researchers continue to work on new ways to treat RA – see the Arthritis Foundation’s research update for information on the latest advances made in studies of arthritis.

Statin Induced Myopathy

Cholesterol is a natural product of the liver
Cholesterol is a natural product of the liver and is necessary for various functions in the body. However, when the liver produces too much cholesterol, it accumulates on the inside of arteries, leading to an increased risk of cardiovascular disease.

Statins reduce the liver´s production of cholesterol
A person’s cholesterol metabolism is complicated and dependent on several factors, for example, genetic make-up, weight and diet. Statins, (also known as HMG CoA reductase inhibitors), are a class of drugs that reduce the liver’s production of cholesterol by blocking the action of a particular liver enzyme (HMG CoA reductase) which is needed to make cholesterol.

Statin drugs can help prevent heart attacks
Statin drugs have been shown to lower the levels of the “bad cholesterol” LDL from 18% to 55% and to raise the levels of the “good cholesterol” HDL (High Density Lipoprotein) from 5% to 15%. Studies have also found that statin drugs can help the body to reabsorb cholesterol that has already accumulated on the inside of artery walls. Statin drugs are therefore useful in helping people avoid their first heart attack. For people who have already suffered a heart attack, they can help prevent further heart attacks.

While generally safe and effective, statins may in some cases cause adverse effects
Statin drugs are generally well tolerated and safe. In the United States they are approved by the Food and Drug Administration (FDA) for lifelong use. More than 100 million people worldwide are on statin drugs to treat high cholesterol levels and prevent heart disease. In rare cases, statin drugs can however cause adverse effects. These include liver problems, muscle weakness or pain – in other words, myopathy. Even more rare is the severe condition known as rhabdomyolysis characterised by rapid muscle breakdown.

Studies indicate that 1 out of every 10,000 persons taking low levels of statins (20 or 40 mg of Simvastatin daily) develops myopathy each year. The incidence increases to as much as 0.9% for those taking higher statin doses (80 mg of Simvastatin daily).

A genetic variant is associated with increased risk of statin induced myopathy
A recent study has identified a genetic variant (rs4149056) in the SLCO1B1 gene on chromosome 12 which is associated with increased risk of developing myopathy in those taking statin drugs. This genetic variant leads to a change in the amino acid sequence of the resulting protein, whereby Valine is replaced by Alanine at amino acid number 174.

The protein encoded by the SLCO1B1 gene is involved in the uptake of various compounds in the liver, including statins. Individuals carrying the C allele of rs4149056 (about 15% of the population), produce SLCO1B1 proteins with a reduced capacity to bind statin in the liver. This means that more of the statin is left circulating in the blood, which in turn can lead to adverse systemic effects like myopathy and rhabdomyolysis.

The study found that individuals carrying two copies of the risk-allele (the CC genotype of rs4149056, occurring in about 2.2% of the population) had a 15% chance of developing myopathy, when taking 80 mg simvastatin per day, in the first year after beginning therapy. For those carrying one copy of the C allele (the CT genotype; about 25% of the population) the chance of developing myopathy was 1.4% and for those carrying no copies of the risk allele (the TT genotype) the chance was 0.3%. Although this study draws its conclusions from simvastatin daily use, the authors suggest these findings are likely to apply to other statins also.

The deCODEme Complete Genetic Scan identifies the rs4149056 sequence variant in the SLCO1B1 gene and provides an estimate of the risk of developing myopathy when taking statin drugs for individuals of European descent.

Please note that this variant only provides information about your genetic propensity in relation to statin-induced myopathy. Many other factors can affect your actual risk of developing myopathy. Thus, not every carrier of the risk allele will develop myopathy. Furthermore, those with no copies of the risk allele may develop myopathy.

If you develop muscle pain or weakness during statin treatment you should consult your physician.

It is essential that any decisions about statin therapy be taken in consultation with a physician.

Brain and nerves:

Alzheimer's Disease

Alzheimer’s disease is characterized by progressive loss of memory
Classical symptoms of Alzheimer’s disease begin with loss of memory for recent events. With time, additional symptoms develop in individuals with the disease, including confusion, disorganized thinking, impaired judgment, trouble with expressing themselves and disorientation.

The main risk factor is increased age
Alzheimer’s disease primarily affects people over the age of 65 and it becomes more prevalent with advanced age. About 5% of individuals in the age range 65-74 are affected by the disease, but nearly half of all individuals over the age of 85.

Certain genes increase the risk of developing Alzheimer’s disease
The risk of developing Alzheimer’s disease is in part genetically determined and rare mutations in three different genes are known to cause early-onset Alzheimer’s, affecting individuals before the age of 65. In addition, a more common variant in the Apolipoprotein E (ApoE) gene called ApoE4 has been shown to increase risk of developing late-onset Alzheimer’s disease.

deCODEme can calculate your genetic risk of developing Alzheimer’s disease
The deCODEme Complete Scan identifies a variant in the ApoE gene and provides interpretation of the associated risk for developing Alzheimer´s Disease in customers of European descent. For people of other ethnicities, currently no data are available for this variant.

Many factors interact to cause Alzheimer’s Disease
Although much progress has been made in understanding the causes of Alzheimer’s, many questions remain unanswered. It is likely that many factors, both inherited and environmental, interact in complex ways to cause the disease. Currently, the main known risk factors are:

• Age: is the greatest risk factor for AD that affects both sexes and most ethnicities.
• Gender: Women are more likely to develop the disease than men, mainly because women live longer.
• Genetics: Close relatives (parents, siblings, children) of individuals diagnosed with AD are at a 3-4 fold greater risk of developing the disease than the general population. Genetic factors therefore play an important role in the development of AD.
• Other known risk factors that may play a role in the development of Alzheimer’s disease are risk factors for cardiovascular diseases (high blood pressure, high cholesterol), educational level and hormone replacement therapy.

Drugs are available for the early stages of Alzheimer’s Disease
Although there is currently no treatment available that can delay or stop the brain degeneration that causes Alzheimer’s disease, several drugs have been approved by the US Food and Drug Administration (FDA) that can temporarily slow worsening of symptoms for 6 to 12 months. As these drugs are mainly useful in the early stages of the disease, some individuals may choose to know their risk factors for the disease.

Lifestyle changes to prevent or slow down Alzheimer’s Disease
The latest medical research suggests that the best hope for preventing or slowing down Alzheimer’s Disease is to adopt a healthy lifestyle that includes protecting your head from injury at all times (e.g. by wearing a seatbelt and using a helmet when biking or skiing) and exercising or stimulating your brain regularly (e.g. by taking a class, learning a new language, playing memory games, or doing crosswords).

Individuals at high risk for Alzheimer’s may benefit from regular screening for early symptoms of the disease by their primary care provider. Early, active medical management, through available treatment options and utilization of programs and support services, can improve quality of life through all stages of the disease for diagnosed individuals and their caregivers.

Essential Tremor

The most common neurological disorder
Also known as ‘benign essential tremor’ or ‘hereditary tremor’, this type of tremor is called ‘essential’, because it occurs in otherwise healthy people and does not have a known cause. Essential tremor (ET) has not been linked to other neurological conditions, is not caused by injury nor is it a side-effect of medication.

Comes in two main forms
This condition comes in two main forms: ET with head tremor and young-onset ET (i.e. that starts at an earlier age than is usual). If ET occurs in more than one member of a family, it is referred to as ‘familial’.

Characterized by hand-tremors when eating and writing
ET is sometimes confused with Parkinson´s disease. However, while Parkinson´s disease is characterized by resting tremor, stiffness and slowness of movement, ET is most frequently characterized by tremors that occur in certain postures of the body, for example in the arms or hands during voluntary movements such as eating and writing. There is sometimes also tremor of the head and voice, but legs are rarely affected. ET can be aggravated by emotional stress, fever, physical exertion, or low blood sugar. ET often impairs writing, drinking, eating and various other activities of daily life.

Many cases of essential tremor are undiagnosed
ET is most often diagnosed between adolescence and 40 years of age, but can develop from childhood and onwards. It is estimated that as many as 5% of people older than 40, and 20% over 65 may have ET. However, many individuals with ET are not diagnosed as such. It is thought that about ten million people have ET in the United States. With the exception of stroke, ET is the most common neurological disorder. It is eight to ten times more common than Parkinson´s disease.

Most cases are largely attributable to genetics
Environmental factors may play a role in the risk of developing ET, but the majority of ET cases are thought to be familial, that is, attributable largely to genetic factors. Linkage studies have identified regions on chromosomes 3q13 (ETM1) (4) and 2p24.1 (ETM2) that are thought to underlie some cases of familial ET. However, the actual sequence variants in these regions have yet to be identified.

deCODE scientists have found a variant associated with FET
Scientists at deCODE genetics have identified a sequence variant, located in the LINGO1 gene on chromosome 15q24.3, that is associated with an increased risk of developing ET. The associated risk was observed in both the familial and sporadic form of ET.

deCODEme can calculate your genetic risk for FET
The deCODEme Genetic Scan identifies this variant and provides an interpretation of the associated risk for the development of essential tremor for individuals of European descent. At this time risk information is not available for other ethnicities.

risk factors for essential tremor largely unknown
The only well-established risk factors for essential tremor are genetic variants and age.

Lifestyle suggestions for people with essential tremor
Essential tremor is not a dangerous or life-threatening condition, but people may find the tremors annoying and embarrassing and if severe, they can adversely affect daily activities and reduce the quality of life. Since the pathology of ET is largely unknown, few recommendations can be provided about how to prevent or delay the onset of the condition. For people who already have ET, the following lifestyle suggestions may, in some cases, help reduce or relieve tremors:

• Avoid stimulants. All stimulants including caffeine and nicotine, may make tremors worse.
• Use alcohol in moderation. Tremors may improve for a short while after drinking small quantities of alcohol, but once the effects of alcohol wear off the tremors tend to worsen.
• Avoid stress. Stress tends to make tremors worse, and relaxing can improve them. Although it may not be possible to eliminate all stress from life, people can learn to change how they react to stressful situations using a range of relaxation techniques. Many people also find that physical exercise can help reduce stress.
• Sleep and rest. Getting enough sleep is very important as fatigue can make tremors worse.

No single treatment works for all
The goal of ET treatment is to minimize functional disability, reduce social handicap, and improve the quality of life. In some cases, people may not require any treatment if their tremor symptoms are mild. There is no one treatment that works for all and sometimes several attempts must be made to find the most effective treatment for each individual. The options available consist of any, or a combination of, the following:

Medications: Currently available medications cannot cure, prevent, or slow the rate of disease progression and are mainly used to reduce symptoms, the most commonly used are:

Beta blockers, a group of medications normally used to treat high blood pressure, can help relieve tremors in some people. They may not be an option for people who also have asthma, diabetes or certain heart problems.

Anti-seizure medications may be effective in people who do not respond to beta blockers.

Tranquilizers are sometimes used to treat people whose tremors worsen with stress or anxiety.

Botox injections, known for reducing facial wrinkles, can also be useful for treating some types of tremors, especially of the head and voice. Botox injections can only improve problems for up to three months at a time.

Physical and/or occupational therapy can sometimes help reduce tremor and improve coordination and muscle control. In some cases using wrist weights can stabilize hands, as can the use of heavier plates, glasses and utensils when eating.

Surgery may be an option for people whose tremors are severely disabling and who do not respond to medications. Deep brain stimulation is the most common surgical procedure, designed to interrupt signals from the thalamus, the area of the brain involved in causing the tremors.

Multiple Sclerosis Risk

Multiple sclerosis is an inflammatory disease of the central nervous system
Multiple sclerosis causes inflammation within the brain and spinal cord (the central nervous system) which destroys myelin, the protective layer that covers the nerves. This can result in multiple areas of scar tissue (sclerosis) and leads to slower or blocked nerve impulses, resulting in the signs and symptoms of MS.

Symptoms of multiple sclerosis can vary greatly
Repeated episodes of inflammation (called flare-ups) can occur in any area of the brain and spinal cord. Symptoms of multiple sclerosis vary greatly and depend upon which areas of the central nervous system are affected, but may include changes in the senses, balance, muscle strength and thinking.

Diagnosing multiple sclerosis involves excluding other diseases
There is no specific diagnostic test for multiple sclerosis. Diagnosis of multiple sclerosis requires clinical evidence of lesions and the exclusion of inflammatory, structural, or hereditary conditions that might result in similar symptoms. The course of the disease varies from minor disability to wheelchair dependency within a few years after disease onset.

The most common neurological disability in young adults
Multiple sclerosis is the most common cause of neurological disability in young adults. Approximately 90% of affected individuals are diagnosed before the age of 60 and most of them are between 20 and 40 years of age. Less than 5% are diagnosed before puberty. The prevalence varies with geography, ethnicity and gender, and is highest in white populations living in temperate regions. In Europe and North America, the prevalence is 1 in 800 (1 in 1200 males and 1 in 600 females), with an annual incidence of 2 to 10 per 100,000 individuals.

Multiple sclerosis is more common in countries with temperate climates
MS is uncommon in Japan, China, and South America. It is practically unknown among the indigenous people of equatorial Africa, native Inuits in Alaska, and Lapps in Scandinavia. Based on a 2007 study of the UK population, 5.3 per 1,000 women and 2.3 per 1,000 men are expected to receive a diagnosis of MS during their lifetime.

Genetic factors contribute to the development of multiple sclerosis
The risk of developing MS is in part genetically determined. Three genetic variants have been found to increase the risk of developing MS. They are located in or near the HLA-DRA gene on chromosome 6, the IL-2Ra gene on chromosome 10, and the IL-7R gene on chromosome 5.

deCODEme can calculate your genetic risk of multiple sclerosis
The deCODEme Complete Scan identifies the three genetic variants listed above and provides interpretation of their associated risk for the development of MS in customers of European descent. Currently no data are available for people of other ethnicities for the variants listed above.

Risk factors for multiple sclerosis
Researchers have not yet found the exact cause of multiple sclerosis, but they have identified the following factors that may increase the risk:

• Ethnicity. MS is more common in people of Northern European descent.
• Environmental factors. Viruses and bacteria have been suspected of contributing to the development of MS. Patients with MS typically have a higher number of immune cells than a healthy person, which suggests that an immune reaction to a viral or bacterial infection might play a role.
• Geographical factors. MS is more common in countries with temperate climates, including Europe, southern Canada, northern United States, and southeastern Australia and New Zealand. The reason for this is unknown, but geographic studies suggest that it may be due to environmental factors, genetic factors, or both.
• Genetics. Although the risk of developing MS in children whose parents are affected by MS is less than 5% over their lifetime, genetic research supports the hypothesis that the tendency to develop MS is inherited. Whether the disease develops however, depends on exposure to environmental triggers.
  

Prevention and treatment of multiple sclerosis
Currently, there is no known way to prevent or cure multiple sclerosis. Many patients do well with no therapy if the disease remains in remission after the initial attack.

Treatment options vary depending on the symptoms of multiple sclerosis
MS causes a large variety of symptoms. For that reason, many different treatments may be necessary to relieve those symptoms. The goal of treatment is to control symptoms, prevent progression of disability, and maintain a normal quality of life.

Medications used for treating MS have serious side effects and carry significant risks, but there are some promising medical therapies on the horizon that may slow the progression of the disease. Additionally, physical therapy, speech therapy, occupational therapy, and support groups can help improve a person’s outlook, reduce depression, maximize function, and improve coping skills.

Nicotine Dependence

Smoking is the leading cause of preventable death, causing approximately five million premature deaths world-wide each year.

One of every six deaths in the United States can be linked to the smoking of tobacco, making this substance more lethal than all other addictive drugs combined.

Nicotine, a component of tobacco, is the primary reason for its addictiveness. However, cigarette smoke contains many other dangerous chemicals, including tar, carbon monoxide, acetaldehyde, nitrosamines, and more. The inhalation of tar increases the risk of lung cancer, emphysema, and bronchial disorders. Carbon monoxide increases the chance of developing cardiovascular diseases. Additionally, secondhand smoke increases the risk of lung cancer in adults and greatly increases the risk of respiratory illnesses in children.

So why do people smoke? Nicotine addiction is what keeps many people smoking despite its harmful effects. In general, addiction is characterized by the compulsive seeking and use of a particular stimulus, even in the face of negative health consequences. It is well documented that most smokers identify tobacco use as harmful and express a desire to reduce or stop using it. Unfortunately, only about 6 percent of people who try to quit are successful for more than a month.

Although the addictive properties of nicotine affect almost all smokers, there are also individual differences in smoking behavior, nicotine dependence, and cessation success. Some of these individual differences have been attributed to genetic factors, prompting a search for susceptibility genes. Recently scientists at deCODE genetics discovered an association between Nicotine Dependence and a specific variant in the genome. The variant is located on chromosome 15 within the nicotinic acetylcholine receptor gene cluster. The variant does not seem to influence the likelihood of whether people start to smoke or not, but among smokers, carriers of the genetic variant smoke more than non-carriers and have higher rates of nicotine dependence, making it more difficult for them to quit. In smokers, this same variant also increases the risk for Lung Cancer and Peripheral Arterial Disease.

The deCODEme Complete Scan identifies the risk variant rs1051730 on chromosome 15 and provides an interpretation of the associated genetic risk for nicotine dependence. Since the genetic variant has not been associated with the initiation of smoking, the associated risk applies only to those individuals who are or have been smokers.

risk factors
Although many associate smoking first and foremost with lung cancer and lung diseases, smoking harms every organ in the body. Cigarette smoking has been linked to about 90% of all lung cancer cases, the number-one terminal cancer in both men and women. Smoking is thought to account for about one-third of all cancer deaths.The overall rate of death from cancer is twice as high for smokers compared to nonsmokers, with heavy smokers having a rate four times greater than nonsmokers. Smoking is also associated with cancers of the mouth, pharynx, larynx, esophagus, stomach, pancreas, cervix, kidney, ureter, and bladder.

Smoking also causes lung diseases such as chronic bronchitis and emphysema, and has been found to exacerbate asthma symptoms in adults and children. More than 90% of all deaths from chronic obstructive pulmonary diseases are attributable to cigarette smoking. It has also been well documented that smoking substantially increases the risk of heart disease, including stroke, heart attack, vascular disease, and aneurysms. It is estimated that smoking accounts for approximately 21% of deaths from coronary heart disease each year.

Additionally, secondary smoke increases the risk for many diseases. It is estimated to cause approximately 3,000 lung cancer deaths per year among nonsmokers and contributes to more than 35,000 deaths related to cardiovascular disease. Exposure to tobacco smoke in the home is also a risk factor for starting to smoke and increased severity of childhood asthma and has been associated with sudden infant death syndrome.

prevention and treatment
The best and most simple prevention is never to start smoking. For people who have already started to smoke, the best prevention is to quit.

Smoking cessation can have immediate health benefits. For example, within 24 hours of quitting, blood pressure and chances of heart attack decrease. Long-term benefits of smoking cessation include decreased risk of stroke, lung and other cancers, and coronary heart disease. A 35-year-old man who quits smoking will, on average, increase his life expectancy by 5.1 years.

Although some smokers can quit without help, many individuals need assistance in quitting. The following treatments are availableto help people quit:

• Nicotine replacement therapies, such as nicotine gum and the transdermal nicotine patch are used (often with behavioral support) to relieve withdrawal symptoms and thereby reduce the discomfort associated with quitting. These treatments provide users with lower overall nicotine levels than they receive with tobacco, hence they do not produce the pleasurable effects of smoking, nor do they contain the carcinogens and gases associated with tobacco smoke.
• Non-nicotine medications, such as the antidepressant bupropion has been shown to help people quit smoking. A more recently approved medication is varenicline , which acts at the sites in the brain affected by nicotine and may help people quit by easing withdrawal symptoms and blocking the effects of nicotine if people resume smoking.Several other non-nicotine medications are being investigated for the treatment of tobacco addiction.
• Behavioral support has been shown to enhance the effectiveness of other treatments and improve long-term outcomes. It includes a variety of methods to assist smokers in quitting, ranging from self-help materials to individual cognitive-behavioral therapy.
  

Scientists are also investigating a nicotine vaccine , which is designed to stimulate the production of antibodies that would block access of nicotine to the brain and prevent nicotine&rquote;s reinforcing effects.

Restless Legs Syndrome:

Restless legs syndrome (RLS) is a common neurological disorder. It is characterized by unpleasant sensations in the legs and an uncontrollable urge to move the legs in an effort to relieve these feelings.

The symptoms are worse during rest or inactivity. Sleep is often interrupted by involuntary periodic limb movements (PLM), which are generally considered to be a hallmark of RLS.

Researchers believe that RLS is commonly unrecognized or misdiagnosed as insomnia or another neurological, muscular, or orthopedic condition. Despite a high number of people affected by RLS in North America and Europe (5% to 15%), the cause is still not clear. Over-indulgent healthcare systems in affluent parts of the world may be more likely to diagnose RLS, and thereby could account for differences in the number of cases reported.

Hereditary factors contribute significantly to the etiology of RLS and four genetic variants have been found that increase the risk of developing RLS. One variant is located in or near the BTBD9 gene on chromosome 6, another in the Meis1 gene on chromosome 2, a third in the region of the MAP2K5/LBXCOR1 gene on chromosome 15 and the fourth in the PTPRD gene on chromosome 9.

The prevalence of RLS is lower in Asia than in North America and Europe and risk variants at all the three RLS loci are also found in lower frequencies in Asian than populations of European descent. The three variants associating with RLS in Europe have not been tested for association with RLS in Asian populations. The lower reported prevalence of RLS in Asia is though most likely a reflection of ethnic differences in frequencies of these risk variants.

The deCODEme Complete Scan identifies the variants listed above and provides interpretation of their associated risk for the development of RLS in customers of northern European descent. Currently, apart from differences in prevalence of the disorder and frequencies of the variants mentioned above, no data are available for people of Asian or African ethnicities, for the three variants listed above.

risk factors

• Age: Although the symptoms of RLS may begin at any age, the syndrome is more common with increasing age.
• Genetics: Approximately 50% of patients with RLS have a family history of the condition, suggesting that genetics is a major risk factor. People with familial RLS tend to be younger when symptoms start and have a slower progression of the condition.
  

Prevention and treatment
Although family history is evident in about 50% of RLS cases, other cases appear to be related to the factors or conditions listed below. Researchers do not yet know if these factors actually cause RLS, although reversing these conditions may improve the symptoms of RLS.

• Low iron levels or anemia may increase the likelihood of developing RLS. Once iron levels are corrected, patients may experience a reduction in signs and symptoms.
• Chronic diseases such as kidney failure, diabetes, Parkinson’s disease, and peripheral neuropathy are associated with RLS. Treating the underlying condition often provides relief from RLS symptoms.
• Pregnancy, some pregnant women experience RLS, especially in their last trimester. For most of these women, symptoms usually disappear within 4 weeks after delivery.
• Certain medications, such as antinausea drugs, antiseizure drugs, antipsychotic drugs, and some cold and allergy medications, may aggravate the disease.
• Researchers have also found that caffeine, alcohol, and tobacco may aggravate or trigger symptoms in patients who are predisposed to develop RLS. Some studies have shown that a reduction or complete elimination of such substances may relieve symptoms, although it remains unclear whether elimination of these substances can prevent RLS symptoms from occurring.
  

Individuals with higher than average risk for RLS and who are experiencing sleep disturbances may benefit from seeking advice from their doctor. Medications such as dopamine agonists may not always be recommended for RLS, particularly if the symptoms are mild. However, important lifestyle changes and activities such as regular sleep habits, relaxation techniques, and moderate exercise during the day, can, in some cases, help reduce symptoms.

Eyes and vision:

Age Related Macular Degeneration

AMD is the most common cause of poor sight in people over 50
Age-related macular degeneration or AMD is a major cause of visual impairment in the United States, with approximately 1.8 million Americans over the age of 50 affected by the disease, and another 7.3 million people with intermediate AMD who are at substantial risk of vision loss. It has been estimated that by 2020 there will be 2.9 million people with advanced AMD in the US.

Mainly the central vision is affected in AMD
As part of the aging process deposits, called drusen, form in the retina of the eye. AMD leads to the deterioration of the retina that is partly due to the excessive accumulation of drusen. The retina is the part of the eye that relays images via the optic nerve to the brain. The centre of the retina is called the macula and is responsible for the detailed central vision that allows people to read, drive, and recognize faces. If the macula starts to break down, areas in the center of the visual field start to look blurred.

The two main types are ‘wet’ and ‘dry’ AMD
AMD can be split into three grades of severity, based on the number and size of the drusen and the appearance of the retina: early, intermediate and advanced, which can be further split into two forms, called wet and dry AMD. Dry AMD is more common than wet AMD, but the latter is responsible for over 80% of cases of severe loss of vision and legal blindness related to AMD. Advanced AMD is primarily a condition affecting individuals after the age of 60.

Genetics contribute significantly to AMD
Genetic factors have been shown to contribute significantly to the development of AMD; for example having first degree relatives with AMD increases the lifetime risk 2-3 fold. Variants in five regions of the genome have been identified that increase the risk of developing AMD: a variant in the CFH gene on chromosome 1, a variant in the ARMS2/HTRA1 genes on chromosome 10, two variants in the C2/CFB genes on chromosome 6 and one variant in the C3 gene on chromosome 19. CFH, C2, CFB and C3 are involved in the immune response and controlling inflammation in the body. Individuals with certain variants in these genes may be at higher risk for inflammation-induced damage to the retina.

deCODEme can calculate your genetic risk of AMD
The deCODEme Complete Scan identifies all the variants listed above and provides an interpretation of the risk for developing AMD in customers of European descent. In East Asians, deCODEme currently identifies risk associated with only a single variant in the ARMS2 gene on chromosome 10. Currently no risk data are available for the variants listed above for people of other ethnicities.

Smoking is one of the main risk factors for AMD
Although it is not clear what causes AMD, a number of factors that may put a person at greater risk for developing AMD have been identified:

• Age: AMD rarely affects those under age 50 and studies show that people over age 60 are at greater risk than other age groups.
• Gender: White females appear to have higher risk than males.
• Smoking: Studies have found that current and former smokers have up to twice the risk of developing AMD as non-smokers.
• Obesity: Studies have suggested a link between obesity and the progression of early- and intermediate-stage AMD to advanced AMD.
• Genetics: The increased risk of AMD related to family history demonstrates that genetics play a significant role in development of the disease. Individuals with a single relative with AMD are twice as likely to develop the disease, while those with two or more relatives are nearly four times as likely to be diagnosed. The risk is even higher if the affected family members were diagnosed before the age of 65.

Early diagnosis and prevention are important
Although there is no known cure for either form of AMD, therapies are available that can slow the progression of the disease. Early diagnosis is also an important part of controlling disease progression. People at risk for AMD, including those over the age of 50 and those with a family history of AMD, should have their eyes examined regularly, learn to recognize the signs of AMD, and take steps to reduce their risk for developing AMD.

Exfoliation Glaucoma

Glaucoma – a group of eye diseases that gradually steal sight
Exfoliation Glaucoma occurs when the fluid pressure inside the eyes slowly rises to abnormal levels because of insufficient recirculation of the fluid of the eye. In glaucoma, deterioration of the optic nerve leads to progressive loss of the field of vision. Open Angle Glaucoma (OAG), which is characterized by painless loss of vision, constitutes the majority of glaucoma cases. OAG may be divided into Primary Open Angle Glaucoma (POAG) and Secondary Glaucoma (SG). POAG is without an identifiable cause of resistance to eye fluid recirculation, whereas in SG the outflow resistance is of a known cause. The most common cause of SG is exfoliation glaucoma that may be responsible for 10 to 30% of all glaucoma, depending on the population.

The leading cause of preventable blindness
Glaucoma is the second most common cause of blindness in the world and is one of the leading causes of preventable blindness. It affects over 60 million people worldwide. Early diagnosis before optic nerve damage, and management of the fluid pressure within in the eye with medication or other treatments may prevent blindness.

Known genetic variants increase the risk of exfoliation glaucoma
Genetic factors are known to contribute considerably to the development of glaucoma. Two sequence variants in a gene called LOXL1 have been found to increase the risk of developing exfoliation glaucoma. The effect is thought to be caused by exfoliation syndrome, which is characterized by accumulation of abnormal deposits on surfaces in the front part of the eye.

deCODEme can calculate your genetic risk of exfoliation glaucoma
The deCODEme Complete Scan identifies variants in the LOXL1 gene and provides interpretation of their associated risk for developing exfoliation glaucoma in customers of European descent. Currently no data are available for people of other ethnicities for the variants listed above.

Risk factors for exfoliation glaucoma
Age, ethnicity and family history are the most important risk factors in the development of glaucoma.

• Age: Glaucoma most commonly affects people over 60 years of age but can begin as early as 30 or 40 years of age.
• Ethnicity. Glaucoma is five times more likely to occur among African Americans than Caucasians and about four times more likely to cause blindness in African Americans compared with Caucasians. Additionally, glaucoma is about 15 times more likely to cause blindness in African Americans between the ages of 45-64 than in Caucasians of the same age group.
• Hypertension. A number of studies also suggest that there is a correlation between glaucoma and high blood pressure.
• Family history/Genetics. Men who have one relative with glaucoma are twice as likely to develop the disease, while those with two or more relatives are nearly four times more likely to be diagnosed. This suggests that genetic risk variants play a significant role in the risk of developing the disease.
  

Early diagnosis is most important
Most people who become blind from glaucoma are already blind on at least one eye by the time of diagnosis, which emphasizes the need for increased awareness and early diagnosis. Studies have shown that the early detection and treatment of glaucoma, before it causes major vision loss, is the best way to control the disease.

High-risk individuals should have regular eye exams
Individuals who may be at high risk for glaucoma include African Americans over age 40; everyone over age 60, especially Mexican Americans; and people with a family history of the disease. These individuals should have a comprehensive eye exam at least once every two years according to recommendations by the National Eye Institute (NEI). Lowering eye pressure in glaucoma’s early stages slows progression of the disease and helps preserve vision.

Preventive treatments are available
A comprehensive eye exam can also reveal other associated eye abnormalities that can increase the risk of glaucoma, such as high eye pressure, thinness of the cornea, and abnormal optic nerve anatomy. In some people with certain combinations of these high-risk factors, eye drops reduce the risk of developing glaucoma by about half. Additional therapies such as laser treatments may be beneficial, especially for the exfoliation form of glaucoma.

Eye- Color

Variation in human eye color
Human eye-color exists on a continuum from the lightest shades of blue to the darkest shades of brown or black. The color range is largely genetically determined by a combination of two forms of melanin produced by melanocytes of the iris.

The colored (pigmented) part of our eyes is the iris, which regulates light exposure to the pupil like the aperture of a camera. The muscles of the iris react to more light by contracting the pupil, and to less light by expanding it. The role of pigmentation in the iris is thought to be similar to the role of pigmentation of the skin, where it protects underlying organs from harmful UV-radiation emitted by the sun.

Why does eye color vary among humans?
The color of the iris is determined by the amount and distribution of the pigment melanin, which is usually dark brown and is produced by a special type of cell called the melanocyte. In simple terms, a brown iris contains abundant melanin (more UV-protection), whereas a blue iris contains much less melanin. Albinos have an almost complete lack of melanin. This results in red or pink iris color, due to the greater visibility of blood vessels through the almost transparent iris. Hence, the eyes of albinos are extremely vulnerable to the sun’s UV-radiation.

Eye color is a relatively simple trait that is primarily determined by one gene
For many decades, eye color has been used in introductory texts about genetics as an example of a human trait that is determined in a simple way by only one gene. The story was that brown eye color was dominant to blue. According to this scheme, if both parents had blue eyes, then all their children would also have blue eyes. However, if one or both parents had brown eyes, then their children could have either blue or brown eyes.

The human iris has indeed many characteristic patterns that have not been fully assessed in genetic studies, but are probably also under strong genetic influences, such as colored spots, borders, furrows etc, that can affect the color appearance of an iris and make color classification of the eye challenging.

The genetics of eye color are more complicated than we used to think, and all the more interesting!
Genetic research has now shown that eye-color is determined by a number of genes. As a result, blue eye color can no longer be viewed as a simple recessive trait. In fact, almost any parent-child combination of eye colors can occur. Nonetheless, one region of the genome plays a more important role than others, so predictions based on the old ‘one gene’ model are correct for most families.

Variants from one region of the genome account for about 75% of the variation in eye color
The actual number of genes that contribute to eye color is not yet fully known. However, it seems that genetic variants in one small region of chromosome 15, containing the genes OCA2 and HERC2, account for about 75% of the overall variation in human eye color. Recent studies have identified variants within the HERC2 and OCA2 genes that are very strongly associated with blue versus brown eye color (article 1, 2, and 3).

The deCODEme Genetic Scan identifies the SNP rs12913832 from the HERC2 gene on chromosome 15, which is strongly associated with blue versus brown eye-color and provides an interpretation of the associated likelihood of blue/grey or brown eye color in individuals of European descent.

Lungs and breathing:

Asthma

Asthma is a chronic lung disease that inflames and narrows the airways
Symptoms of Asthma include difficulty in breathing, wheezing, coughing, and a feeling of tightness in the chest. Asthma can be mild, with signs and symptoms occurring only with exercise or exposure to an allergen, or it can be severe and require frequent hospitalizations. In rare but very severe cases, asthma can be deadly.

Asthma affects people of all ages, but most often starts in childhood
Asthma is a common chronic disease, affecting over 300 million people around the world. Onset of asthma typically begins in childhood but it can also start later in life (adult onset). Approximately 1 in every 10 people will develop asthma during their lifetime. In the United States, about 20 million people have been diagnosed with asthma; of these, nearly 9 million are children.

Genetics contribute to the risk of developing asthma
Genetic factors are known to play a significant role in the development of asthma. Three common genetic variants, on chromosomes 2 (in the IL1RL1 gene), 9 (near the IL33 gene) and 17 (near the ORMDL3 gene), have been associated with an increased risk of developing asthma.

deCODEme can calculate your genetic risk of asthma
The deCODEme Complete Scan identifies the above mentioned variants and provides an interpretation of the associated risk of developing Asthma in individuals of European descent. For individuals of east Asian descent, the risk of developing asthma associated with the variants on chromosomes 2 and 17 is calculated. Currently, no risk data for the three variants is available for people of other ethnicities.

Environmental factors and genetics are thought to cause asthma
Although the cause of asthma is not currently known, studies have shown that some groups of individuals may be at greater risk of developing asthma than others. The main risk factors for asthma are:

• Environmental risks: Risk of asthma may be higher in individuals who are regularly exposed to allergens, smoke, or chemicals; live in urban areas; or have a history of repeated respiratory infections during their childhood.
• Ethnicity: African Americans have higher rates of asthma than Americans of European descent.
• Age: Although asthma affects people of all ages, it often starts in childhood.
• Gender: Before puberty, asthma is more common among boys than among girls, but after adolescence more women than men are affected.
• Genetics: The risk for developing asthma is increased three- to six-fold in people who have a parent with asthma.

Asthma can’t be cured, but its symptoms can be controlled
Asthma symptoms can be caused by allergens or irritants that are inhaled into the lungs, resulting in inflamed, clogged, and constricted airways. Symptoms related to asthma can also be triggered by respiratory infections, exercise, cold air, tobacco smoke and other pollutants, stress, food, or medications.

Individuals with asthma can decrease their symptoms by avoiding these triggers and by adhering to their prescribed treatments.

Various asthma medications can help manage asthma symptoms
Treatment is primarily aimed at avoiding known allergens and respiratory irritants and controlling airway inflammation with medications. With early diagnosis and preventive treatment, most asthma patients can expect to enjoy a good quality of life.

Heart and circulation:

Abdominal Aortic Aneurysm

AAAs are bulges in weakened sections of the aorta
The aorta is the body´s largest artery, carrying blood from the heart to smaller branch arteries. An aortic aneurysm is an abnormal weakening of parts of the aorta. The pressure from blood flowing through the aorta can cause the weakened part to bulge. An aneurysm can stretch the aorta wall to the extent that it finally bursts or ruptures. A ruptured aneurysm can cause severe internal bleeding and leads to death in over 65% of instances. Fortunately, especially when diagnosed early, an aortic aneurysm can be treated, or even cured, with highly effective and safe treatments.

The two main types are abdominal and thoracic
There are two main types of aortic aneurysms, thoracic and abdominal, depending on which part of the aorta is affected; the upper part that traverses the chest (thoracic aortic aneurysm or TAA) or the lower part that traverses the abdomen (abdominal aortic aneurysm or AAA). About three in four of all aortic aneurysms are AAA.

Most AAAs are without symptoms until rupture or near rupture
In most cases individuals experience no symptoms at all or only vague symptoms of AAA until the aneurysm is near rupture or ruptures. Therefore the true prevalence of AAA is not known, but it is estimated that 1.5% to 9% of men and 1% to 2% of women have this condition. The rupture of AAA causes roughly 15,000 deaths every year in the United States.

Genetics contribute to the risk of developing AAA
Research suggests that AAA has a strong familial component. This indicates that there is an important genetic contribution to the risk of developing AAA. Our scientists at deCODE genetics have identified a common genetic variant on chromosome 9 that is associated with increased risk of AAA (See Helgadottir et al, 2008).

deCODEme can calculate your genetic risk of AAA according to the best science available to date
The deCODEme Complete Scan identifies the variant on chromosome 9 and provides an interpretation of the risk of developing AAA for individuals of European ancestry. The same variant also increases the risk of Heart Attack in individuals of both European and Asian ancestry and Intracranial Aneurysm in European individuals. At the present time, information about the risk of AAA conferred by this genetic variant on individuals of other ethnicities is not available.

AAAs are most common in men older than age 65 years, people with high blood pressure, and smokers
Although the ultimate causes for AAA are still unclear, the known risk factors are:

• Age and gender: AAA is most commonly encountered in older men. The condition is 2-5 times more common in men than women and the incidence increases with age in both sexes. In populations over age 60, estimates of prevalence range from 2% to 8%. AAA is uncommon in both men and women younger than 50 years of age.
• Smoking: Smoking is the single most important environmental risk factor and the more you smoke, the greater the risk. This is probably because the underlying cause for most AAA is atherosclerosis of the aorta, which is exacerbated by smoking. Research has shown that the prevalence of AAA in tobacco smokers is more than four times that of life-long non-smokers.
• Other cardiovascular risk factors: Some cardiovascular risk factors such as high blood pressure and abnormal cholesterol levels have been associated with AAA, whereas others, such as diabetes, have not.
• Ethnicity: AAA is diagnosed less frequently in Asians and African-Americans than individuals of European descent.
• Genetics: Genetic factors have a recognized impact on the development of AAA, with 15-20% of affected individuals reporting a family history of the condition. The lifetime risk of AAA in a first degree relative (parent, child or sibling) of a patient with AAA is 11-28% or 3-7 times that of the general population (with a lifetime risk of 4%).

Not smoking is the single most important prevention strategy
The single most important prevention strategy is not to smoke and to stop smoking if you do. A healthy lifestyle in general is recommended, including regular exercise and maintenance of a normal weight.

The American College of Cardiology recommends a screening abdominal aortic ultrasound for men 60 years of age or older who are either siblings of AAA patients or have parents with AAA as well as for male smokers (current and former smokers) between 65 and 75 years of age.

When diagnosed early, an AAA can be successfully treated
In all patients with recognized AAA, blood pressure and cholesterol control is recommended and generally, surgical repair is planned for all aneurysms which are 5.5 centimeters (2.2 inches) and larger as well as all symptomatic AAA regardless of diameter. Urgency of surgical repair depends on the risk of rupture.

Atrila Fibrillation

Atrial fibrillation is the most common heart-rhythm disturbance
An estimated 2.3 million American adults have been diagnosed with atrial fibrillation and the risk of developing this condition at any time after the age of 40 has been found to be 20-25% in individuals of European and East Asian descent.
The irregular and often rapid heart rate can result in poor blood flow
Atrial fibrillation is caused by disruption of the normal functioning of the electrical system in the atria, the two upper chambers of the heart. Normally the electrical system stimulates the atria to contract regularly and in coordination with the ventricles, the lower chambers of heart. In atrial fibrillation the atria are stimulated to contract very irregularly and rapidly, up to 350 to 600 times per minute. This results in ineffective and uncoordinated contraction of the atria – the atria essentially quiver instead of contracting. Although a natural checkpoint between the upper and lower chambers protects the ventricles from overstimulation, the contraction rate of the ventricles (which is the same is the actual heart rate or pulse) is still irregular in atrial fibrillation and can be up to 220 beats per minute when not treated. Occasionally the pulse rate is very slow, necessitating pacemaker placement.

Symptoms range from none to serious discomfort
It is possible to have atrial fibrillation without feeling the symptoms generally associated with this condition. Usually, the symptoms of atrial fibrillation include heart palpitations, fatigue, dizziness, tightness in the chest and shortness of breath. Atrial fibrillation can also worsen symptoms due to other heart diseases such as heart failure and coronary artery disease. Some individuals are always in atrial fibrillation (chronic or permanent atrial fibrillation) while others have episodes of the condition.

Genetics contribute significantly to the risk of atrial fibrillation
Genetic variants are known to contribute to the risk of atrial fibrillation and up to a third of patients with AF have a family history of the disease. Scientist at deCODE genetics have discovered two common genetic variants that increase the risk of AF; near the PITX2 gene on chromosome 4 and in the ZFHX3 gene on chromosome 16.

deCODEme can calculate your genetic risk of atrial fibrillation
The deCODEme Complete Scan identifies both risk variants in individuals of European descent and the chromosome 4 variant in idividuals of East Asian descent and provides interpretation of the associated risk for developing atrial fibrillation. Information regarding the association of these variants with AF in people of other ethnicities is currently not available.

Atrial fibrillation mostly occurs as a result of another cardiac condition
Risk factors for developing atrial fibrillation include:

• Age: Atrial fibrillation becomes significantly more common with increasing age. It is relatively rare in individuals younger than 60 (less than 1%) but common in those older than 80 (over 10% in Caucasians).
• Cardiovascular disorders: High blood pressure is the most common condition associated with atrial fibrillation and is a very important risk factor. Heart failure and heart valve disease are other disorders often associated with atrial fibrillation and it is also very commonly seen following heart surgery.
• Several other conditions are known to cause episodes of atrial fibrillation. These include hyperthyroidism (overactive thyroid), pulmonary embolus (blood clot in the lung), alcohol, stimulants such as cocaine or decongestants, surgeries, infections and other acute illnesses. Other factors that have been shown to increase the risk of atrial fibrillation include obesity and the sleep apnea syndrome.
• Genetics: Several distinct regions of the genome and gene mutations have been linked to atrial fibrillation in individuals and families but these appear to be rare causes. On the other hand, common genetic variants have been identified on chromosome 4 that increase the general population risk of developing atrial fibrillation.
  A heart-healthy lifestyle can prevent atrial fibrillation
  

Prevention of atrial fibrillation is a challenging task. Steps you can take to decrease the likelihood of developing atrial fibrillation include maintaining a healthy weight, avoiding stimulants and using alcohol in moderation. Optimal management of high blood pressure and other heart disorders will help prevent atrial fibrillation and certain medications can be used to decrease its incidence after heart surgery.

Treatment depends on severity and frequency of symptoms
The feared complication of atrial fibrillation is stroke. The electrical disturbance and quivering of the atria promote blood clot formation in the upper chambers of the heart. If a clot forms, the danger is that the clot, or parts of it, can travel with the bloodstream to the brain or other organs (embolize). An embolic stroke will occur if the clot blocks one of the arteries supplying blood to the brain. Compared to other types of strokes, embolic strokes are generally more severe and more commonly recur. Atrial fibrillation is associated with a significant four to five-fold increase in the risk of stroke and accounts for one third of all strokes in patients older than 65.

The main goal of treatment is to prevent stroke
The goals of atrial fibrillation treatment include stroke prevention, restoration of normal heart rhythm and heart rate control. The treatment can be challenging and should be designed to meet the needs of each individual patient. The specific type of treatment depends on the contributing causes of atrial fibrillation, coexisting heart disease, if the disease is episodic or permanent and if the symptoms are interfering with daily activities and quality of life. Restoration of normal heart rhythm is often not possible. Anticoagulation (thinning of the blood) for stroke prevention is generally recommended for all patients older than 65 as well as younger patients who also have hypertension or other cardiovascular diseases.

Heart Attack

Coronary heart disease can result in a heart attack
The heart is a hard-working muscle that pumps blood throughout the body. To function properly, the heart muscle needs oxygen, which is supplied by the coronary arteries wrapped around the surface of the heart. In coronary heart disease, the build-up of fat, cholesterol, and other substances collectively referred to as plaque, on the inner lining of the coronary arteries causes them to become thicker, harder, and narrower. This disease process is known as atherosclerosis. If the build-up of plaque within a coronary artery cuts off blood flow to the heart muscle, a heart attack occurs.

A heart attack damages the heart muscle
A heart attack, also called myocardial infarction (MI), is a serious event. When a coronary artery is completely blocked a portion of the heart muscle is deprived of a necessary supply of oxygenated blood, which can cause serious damage in a matter of minutes. Depending on how much of the heart muscle is damaged, heart function can be anywhere from mildly to severely impaired. Severe heart attacks, accompanied by extensive damage to the heart muscle, can result in heart failure and even death.

deCODEme can calculate your genetic risk of heart attack
The deCODEme Complete Scan identifies eight common genetic variants associated with an increased risk of heart attack. One variant on each of the following chromosomes: 2, 3, 6, 9, 10 and 12 (SH2B3 gene) and two variants on chromosome 1. The variant near the CDKN2A/2B genes on chromosome 9 is a particularly strong risk factor for early-onset heart attack (occurring earlier than 50 years of age in men and 60 years of age in women). A variant in the BRAP gene on chromosome 12 contributes to the risk of heart attack in East Asians but not people of European descent.

Preventing a heart attack starts with assessing your risk
The American Heart Association recommends that heart attack prevention should begin by age 20 and emphasizes that prevention starts with assessing your risk factors and working to keep your overall risk low.

Genetic risk is part of the overall risk of heart attack
Several studies have found evidence of a genetic contribution to coronary heart disease and heart attack. Knowing your genetic risk of heart attack can help you assess your overall risk, which is the first step in planning your preventive and heart-healthy lifestyle. Remember, that studies have shown that your lifestyle is your best defense against coronary heart disease and heart attack.

The deCODEme heart attack risk calculation identifies the eight variants listed above in customers of European descent and provides interpretation of their associated risk for the development of coronary heart disease and heart attack as well as early-onset heart attack (CDKN2A/CDKN2B). In East Asians, deCODEme identifies the variant on chromosome 9 and the BRAP gene variant on chromosome 12. See scientific details for more information.

At the present time, no risk estimation data are available for people of other ethnicities for the variants listed above.

Please note that the deCODEme scan does not identify rare gene variants linked to the extreme heritable forms of coronary heart disease which greatly increase the risk of heart attack.

Intracranial Aneurysm

Bulges in weakened sections of brain arteries
When a weak area of an artery supplying the brain with blood expands or bulges, it is called an intracranial aneurysm (also known as a brain aneurysm). The feared complication of this type of aneurysm is rupture of the weakened vessel wall, causing bleeding in the area between the brain and the surrounding arachnoid membrane (called a subarachnoid hemorrhage). This is a medical emergency that may result in brain damage or death. Prior to rupture, most intracranial aneurysms are without symptoms, but may in some cases cause severe headaches, double vision, seizures, or vomiting.

Most are without symptoms and never diagnosed
It is estimated that intracranial aneurysms can be found in 2-3% of the adult population. Most of these never rupture, are without symptoms, and are never diagnosed. The estimated incidence of ruptured intracranial aneurysms ranges from two to 22 cases per 100,000 individuals per year. Up to half of those who experience a rupture of intracranial aneurysms and the consequential subarachnoid hemorrhage die and a third of survivors suffer moderate to severe disability.

Genetic factors play a recognized role
Genetic factors play a recognized, albeit not yet fully known role, in the development of intracranial aneurysms. About one in every 10 patients with a subarachnoid hemorrhage has a family history of intracranial aneurysms and those who have a family history are usually younger at the time of diagnosis and more commonly have multiple and large aneurysms. Scientists at deCODE genetics and others, have identified three common genetic variants that associate with increased risk of intracranial aneurysm; two on chromosome 8 and one on chromosome 9.

deCODEme can calculate your genetic risk for intracranial aneurysm
The deCODEme Complete Scan identifies the three variants and provides an interpretation of the risk of developing this type of aneurysm for individuals of European ancestry. For East Asians, the deCODEme Genetic Scans can only provide risk calculations for the variant on chromosome 9. At the present time no risk data are available for people of other ethnicities for the variants listed above.

The variant on chromosome 9 also increases the risk of Heart Attack in individuals of both European and Asian ancestry and increases the risk of Abdominal Aortic Aneurysm in individuals of European descent. At the present time, risk of intracranial aneurysms conferred by this genetic variant on individuals of ethnicities other than European, is not available.

Risk factors

• Age and gender. Intracranial aneurysms can occur in all age groups but are most commonly detected in individuals between the ages of 40 and 60. The average age of a ruptured or bleeding intracranial aneurysm is 50 years of age.
• Hypertension. High blood pressure increases the risk of intracranial aneurysms and of their bleeding.
• Other. Smoking, alcohol abuse, and cocaine use have been associated with intracranial aneurysms. Rare causes include infections, connective tissue disorders and trauma.
• Ethnicity. Studies have indicated that subarachnoid hemorrhage is less common in individuals of European descent than in African-Americans, Asians and Hispanics.
• Genetics. Autosomal dominant polycystic kidney disease and various other rare hereditary conditions, are associated with intracranial aneurysms. Additionally, about 10% of patients diagnosed with an intracranial aneurysm, have a first-degree family member also with the condition. A family history of intracranial aneurysms has been found to be equally common among individuals of European descent, African-Americans and Hispanics.
  

Treatment depends on size and location of the aneurysm
Intracranial aneurysms can be treated with either open surgery or minimally invasive endovascular methods (the aneurysm is treated through thin plastic tubes or catheters inserted in a groin artery). Ruptured aneurysms are generally treated immediately to prevent further tears and bleeding. Whether treatment is recommended for asymptomatic and incidentally diagnosed aneurysms depends on the size and location of the lesion.

Screening is only recommended for high-risk individuals
Screening has been recommended for patients with autosomal dominant polycystic kidney disease and for those who have two immediate relatives with intracranial aneurysms (although the latter indication remains controversial).

Peripheral Arterial Disease

PAD reduces blood-flow to head, arms, and legs
In peripheral arterial disease (PAD) the arteries that carry blood to the head, organs, or arms and legs, become narrowed or blocked due to fatty deposits on their inner lining. This atherosclerotic process is similar to the one that leads to coronary heart disease (CHD) and indeed, people with PAD sometimes also suffer from CHD. Peripheral arterial disease can occur in arteries anywhere in the body outside the heart, but most commonly in those of the legs and pelvis.

Early symptoms include leg pain when walking
The narrowing of arteries compromises normal blood flow and causes symptoms which vary with the severity of the disease. The earliest symptoms of PAD include leg pains and cramping associated with physical activity that subside with rest. This characteristic symptom of PAD is called claudication.

Insufficient blood flow can cause tissue damage
Severe disease in the legs can cause continuous pain and ulcers due to insufficient blood flow resulting in tissue death (gangrene) and amputation. Over 200,000 surgical and vascular (angioplasty) procedures are performed each year in the United States to prevent the onset of severe tissue damage in PAD.

Many mistake their symptoms for something else
It is estimated that PAD affects over 10% of the adult population in the industrialized world and one in five over the age of 75. In the United States about eight million people over the age of 40 are thought to have PAD. The condition often goes undetected as the symptoms can be elusive or absent.

Risk factors include environmental factors and genetics
Various factors are considered to contribute to the risk of developing of PAD, including environmental factors, of which smoking is considered the most significant. Less is currently known about the impact of genetics although it is generally believed that many genetic variations play a role and that each has a small or modest individual effect on disease development.

A known genetic variant is associated with increased PAD risk
Scientists at deCODE genetics have discovered an association between the diagnosis of PAD and a specific variant in the genome. The variant is located on chromosome 15 within the nicotinic acetylcholine receptor gene cluster. In smokers, this same variant also increases the risk for Nicotine Dependence and Lung Cancer.

deCODEme can calculate your genetic risk
The deCODEme Complete scan and the deCODEme Cardio scan identify the risk variant rs1051730 on chromosome 15 and provides interpretation of the associated risk for development of PAD in individuals of European descent. Insufficient information is currently available about the association of this variant to PAD in individuals of other ethnicities.

Risk factors for PAD
Various factors are considered to contribute to the development of PAD, of which the following are considered most significant:

• Smoking. The single most important risk factor for peripheral arterial disease is smoking.
• Age and gender. Peripheral arterial disease is more common in men than women and the incidence increases with age.
• Other cardiovascular risk factors. In addition to cigarette smoking, diabetes and high blood pressure are significant risk factors. Abnormal cholesterol levels are also associated with the disease.
• Ethnicity. Peripheral arterial disease is more common in African-American and Hispanic individuals than those of European or Asian descent.
  

Not smoking and exercising are important prevention strategies
In relation to PAD the importance of a healthy lifestyle cannot be overstated. Regular exercise and not smoking are the two most important steps in both prevention and treatment. Other interventions include risk factor management, medications and surgeries.

• Risk factor management: Never to start smoking – or stopping if you do smoke – is the single most important step in prevention and treatment of PAD. This cannot be emphasized enough. Other interventions include treatment of high blood pressure, high cholesterol and diabetes. Equally important is a structured exercise program which is often the most effective treatment for symptoms of PAD.
• Medication: Most patients are prescribed a weak blood thinner such as aspirin or clopidogrel to prevent blood clot formation and in some cases the medications cilostazol and pentoxifylline may help alleviate symptoms and increase walking distance.
• Surgical interventions: Bypass surgery or less invasive percutaneous procedures such as angioplasty can be recommended when noninvasive therapies have failed to improve symptoms. The choice of procedure depends on lesion characteristics and the surgical skills available.
  

Digestive and metabolic system:

Alcohol Flush Reaction

An unpleasant response to drinking alcohol
Some people experience an unpleasant reaction to drinking even a slight amount of alcohol. Their face turns red, and sometimes they also have signs of drowsiness, increased heart rate, nausea, and symptoms of reduced blood pressure. This reaction to alcohol is most commonly seen in individuals of East Asian ancestry, which is why it is sometimes referred to as the "Asian Flush".

Occurs when the body cannot break down ingested alcohol
Alcohol is toxic to human bodies. In people who do not experience alcohol flush reaction, alcohol is broken down (metabolized) in the liver into substances which can be either used or excreted by the body. This breakdown occurs in several steps. First the enzyme alcohol dehydrogenase (ADH) converts alcohol to acetaldehyde. Acetaldehyde is a substance even more toxic to the body than alcohol and contributes largely to the adverse effects of alcohol generally known as a “hangover”. Second, acetaldehyde is broken down into the harmless acetic acid (or vinegar) by another enzyme called aldehyde dehydrogenase-2 (ALDH2). A third enzyme finally breaks the acetic acid into fat, carbon dioxide, and water. The impaired function of any of these critical enzymes disrupts alcohol metabolism, leading to varying degrees of discomfort depending on the amount of alcohol ingested and which enzyme is affected.

A known genetic variant is the major cause for alcohol flush reaction
Alcohol flush reaction is largely due to a genetic variant that affects one of the enzymes responsible for breaking down (metabolizing) alcohol. This genetic variant is found in the ALDH2 gene and is known as the ALDH2*2 allele. The ALDH2 gene regulates the production of the enzyme aldehyde dehydrogenase 2 that has the role of transforming acetaldehyde into acetic acid. The ALDH2*2 allele is dominant. This means that even one copy of it interferes with the formation of a fully functional ALDH2 enzyme, with the result that acetaldehyde cannot be broken down and builds up in the body when drinking alcohol, leading to the symptoms described above.

The ALDH2*2 variant is common in individuals of East Asian descent (45-50%), but is extremely rare in most non-Asian populations.

deCODEme can assess your genetic risk for alcohol flush reaction
The deCODEme Complete Scan identifies the sequence variant (rs671) in the ALDH2 gene on chromosome 12 and gives an interpretation of the associated genetic risk for alcohol flush reaction. It does not at this time identify the sequence variants associated with the defective ADH enzyme in the first step of alcohol breakdown.

Please note however that alcoholic beverages are often a complex mixture of grape, yeast, hop, barley or wheat-derived substances and preservatives. Regardless of the results of the deCODEme genetic scan, if you experience the described symptoms associated with alcohol flush reaction you could be sensitive to other substances in alcoholic beverages or you may be on a medication that interacts with alcohol in this way.

The benefits to having alcohol flush reaction
Having the genetic variant(s) predisposing individuals to alcohol intolerance also has an advantage; these individuals may be protected against developing alcoholism, at least partly due to the fact that they often choose to avoid alcoholic beverages altogether. Studies have indeed shown that people of Asian descent, as a whole, have lower rates of alcohol dependence compared with other ethnic groups. In fact, the knowledge behind the alcohol flush reaction has been utilized in therapeutics for alcoholism. Doctors sometimes prescribe alcoholics with a drug called disulfiram which essentially mirrors the ALDH2*2 effect (inhibits the ALDH2 enzyme) and hence discourages use and abuse of alcohol.

Bitter Taste Perception

Taste perception – more than a matter of taste!
Taste is one of the senses through which humans perceive their environment. Most families have at least one fussy eater, so we know from experience that taste perception varies considerably between individuals and populations.

Taste perception is partly determined by genetics
These differences in perception depend to some extent on the kind of foods we become accustomed to during childhood. However, there is more to taste than meets the eye (or tongue!). Scientists think that much of taste perception is genetically determined.

There are five main categories of taste
There are essentially five main categories of taste; sweet, sour, salty, bitter, and umami. Umami is a Japanese term for the savory taste sensation triggered for example by the amino acid glutamate, which is naturally present in meat, poultry, seafood and vegetables, and is also found in the flavor enhancer monosodium glutamate.

Harmful substances are often bitter-tasting
Taste is perceived in taste receptors on the tongue surface, commonly known as taste buds. From an evolutionary perspective, the ability to distinguish between different chemicals in food and drink is crucial for the survival of humans and all other animals. Thus, individuals who perceive an unpleasant taste when attempting to ingest harmful foods are more likely to survive and reproduce, and even more so if they are also drawn to highly nutritious food because of a perception of pleasant taste.

Nutritious foods tend to have pleasant tastes
Accordingly, foods that have a pleasant taste tend to be nutritious and contain substances that are good for us, such as sugars, salts and proteins. Salty and sour detection helps to control the salt and acid balance of the body, our positive perception of sweetness ensures that we consume food that is rich in calories, and umami is thought to attract us to protein-rich foods. Conversely, things with an unpleasant taste tend to contain substances that are detrimental to our health or dangerous concentrations of useful substances.

Bitter taste perception has evolutionary advantages
A key element of unpleasant taste is the perception of bitterness. It is likely that this category of taste evolved in animals to help them avoid eating plants and other foods containing toxins and other harmful chemicals. It is a testament to the power of natural selection that such substances are typically perceived as bitter-tasting by humans.

There are non-tasters, tasters, and super-tasters of bitterness
Not all humans have the same perception of bitterness for some substances. An intriguing example is the case of substances that are chemically similar to phenylthiocarbamide (PTC) and propyl-thiouracil (PROP). Such compounds are for instance found in cabbage and rapeseed. Some people perceive no particular taste of these compounds ("non-tasters"), whereas others experience an extremely unpleasant bitter taste ("tasters"). Among tasters there is also variation, in that some tasters (so-called "super-tasters") are extra sensitive to bitterness. The frequency of tasters and non-tasters varies considerably among human populations. Thus, the frequency of non-tasters ranges from 3% in West Africa; 6-23% in China, 40% in India and is estimated to be around 30% in people of European descent.

Genetics explain about 20% of variance in bitter taste perception
The cause of differences in the perception of PTC-like compounds among humans has been traced to genetic variants in the TAS2R38 gene on chromosome 7. If you are a “taster” of bitterness, you are likely to carry the C allele of the SNP rs1726866. The C allele is dominant, so having one copy is enough to have the perception of a bitter taste. On the other hand, if you have the T allele of this SNP on both copies of chromosome 7, then you have about an 80% chance of being a "non-taster" of bitterness in response to PTC-like compounds. This means that foods that may taste bitter to others taste far less bitter to you. It is thought that about 20% of the variation in bitter taste perception of these compounds is explained by other genetic variants.

deCODEme can assess whether you are a non-taster, taster, or super-taster of bitterness
The deCODEme Complete Scan identifies the SNP rs1726866 in the TAS2R38 tasting gene on chromosome 7 and gives an interpretation of the associated likelihood for being a "taster" or "non-taster" of bitterness in reaction to PTC-like compounds.

The science of taste is a growing area of research
Understanding the diversity of the bitter-taste perception and the genetics of taste is a growing area of research. It has implications beyond the physiology of taste itself and increased understanding of human evolution is one of the goals.

Taste perception has considerable effects on nutrition and health
Taste perception and the genetically determined human response to bitter-tasting foods may also have a considerable effect on nutrition and health. Studies have for example found that the non-taster genotype is a predictor of increased alcohol consumption in adults and also associated with lower preferences for sweetness in children and may therefore reduce their likelihood of dental decay. Studies have also found that "supertasters" find some foods too bitter to enjoy, for example grapefruit, coffee and tea, brussel sprouts and cabbage. They may also be more sensitive to sweetness and much less likely to tolerate hot and spicy foods. Future studies will improve our understanding of the origin and the implications of these various taste perceptions for nutrition and health.

Celiac Disease

Celiac disease is caused by an abnormal immune reaction
Celiac disease (CD) (also known as coeliac disease, celiac sprue, nontropical sprue, and gluten sensitive enteropathy) is caused by an abnormal immune response to wheat gluten and similar proteins in barley and rye. Some people with CD may also have a reaction to oats. The immune reaction results in injury to the tissues lining of the inside of the small intestine that can interfere with the ability to absorb nutrients from food.

Symptoms vary between individuals
CD symptoms range from mild to severe and can include fatigue, anemia, diarrhea, abdominal discomfort, weight loss, vomiting, and mouth ulcers. In children, CD can stunt growth and have a significant impact on overall development. If left untreated, the disease can lead to other serious conditions, such as osteoporosis (thinning of the bones), infertility, and certain types of cancer.

Celiac disease can be difficult to diagnose
Until recently, CD was thought to be uncommon in the United States. However, recent studies estimate that about 2 million people in the United States have CD, or about 1 in 133 people. Among people who have a first-degree relative diagnosed with CD, 1 in 22 people may have the disease. As many individuals with CD have no or mild symptoms, it is estimated that for every adult individual who is diagnosed with CD, there are eight cases that go undetected.

Several genetic variants are associated with celiac disease
Several genetic variants have been found to contribute to the risk of developing CD; most importantly a variant in the HLA-DQA1 region on chromosome 6. The other variants are in or close to the following genes: RGS1 on chromosome 1, IL1RL1 / IL18R1 / IL18RAP / SLC9A4 on chromosome 2, CCR1 / CCR3, IL12A / SCHIP1 and LPP on chromosome 3, IL2 / IL21 on chromosome 4, TAGAP on chromosome 6 and SH2B3 / ATXN2 on chromosome 12.

deCODEme can calculate your genetic risk
The deCODEme Complete Scan identifies the variants listed above and provides information on the associated risk for the development of CD in individuals of European descent. At the present time data are not available for people of other ethnicities for these variants.

The strongest known risk factors is genetics

• Genetics: The strongest known risk factor for CD is genetics. Studies of identical twins (who share 100% of their genome) have shown that if one twin has CD, the likelihood that the other twin also has the disease is 70-75%. For non-identical twins (who share 50% of their genome) the likelihood that both will have CD is about 10%. Among genes that appear to increase the risk of developing CD are HLA-DQA1 and IL2/IL21.
• Other risk factors: In some cases, CD develops following surgery, pregnancy, childbirth, viral infection, or severe emotional stress.

Prevention and treatment
Blood tests are available to aid in the diagnosis of CD. It is recommended that individuals with a family history of CD or who are experiencing digestive symptoms, including chronic diarrhea, weight loss despite normal eating levels, or abdominal distention, be tested for CD. Breastfeeding in infancy and delayed introduction (after 3-6 months of age) of gluten in the diet may protect against the development of celiac disease in at-risk individuals.

A gluten-free diet is currently the only accepted therapy for CD. It carries few risks and in most individuals it is highly effective.

Crohn's Disease

A chronic disease of the digestive system
Crohn’s disease (CD) is a chronic inflammatory disease in which the body’s immune system overreacts, causing inflammation of the intestine. Crohn’s disease can associate with other health issues, such as liver problems, arthritis, and skin and eye problems.

Mostly affects the lower part of the small intestine
Crohn’s disease can affect any part of the gastrointestinal tract but most commonly it affects the end of the small intestine (the ileum) and the beginning of the large intestine (the colon). All layers of the intestine may be involved and between patches of diseased bowel there can be normal healthy bowel.

Also referred to as an inflammatory bowel disease
Along with Ulcerative colitis (UC), these diseases are referred to as Inflammatory bowel disease (IBD). In rare cases, patients have been diagnosed with both CD and UC, a condition called Crohn’s Colitis.

People with CD tend to have abnormalities of the immune system
While the exact chain of events that lead to Crohn’s disease is unknown, it is believed to be an autoimmune disease. The abnormal immune response and inflammation of the intestine lead to bloody diarrhea, abdominal pain, and weight loss. The symptoms of CD disease vary in severity and onset, they may start gradually or suddenly.

Is most common in Europe and North America and runs in families
The risk of developing CD in one’s lifetime is 0.5% with an estimate of 400,000 to 600,000 people in North America developing CD each year. Crohn’s disease is most commonly observed in Europe and North America and the number of cases has increased over the last several decades.

Genetics play a significant role
Genetic factors are known to play a significant role in the development of CD. To date 29 genetic variants have been found that increase the risk of developing CD. One variant is located on each of the following chromosomes: 2, 3, 7, 8, 11, 13, 16 and 18 and more than one variant is located on the following chromosomes: 1, 5, 6, 9, 10, 17, 21. Of these, four variants, on chromosomes 1, 3, 10 and 18, have also been associated with increased risk of developing ulcerative colitis.

deCODEme can calculate your genetic risk of Crohn’s disease
The deCODEme Complete Scan identifies the 29 variants listed above and provides interpretation of their associated risk for developing CD in customers of European descent. Currently no risk data are available for people of other ethnicities for the variants listed above.

Risk factors
The true causes of Crohn’s disease (CD) are unknown, but it seems that the immune system may be provoked by many factors, including respiratory infections or physical stress.

• Age: The prevalence of the disease is highest during the second and third decades of life, but CD can occur in people over 70 years and in childhood, although it is not common in children younger than 15 years.
• Ethnicity: Individuals of European decent are at greater risk of developing CD than other ethnic/racial groups.
  Smoking: Smoking adds to the risk for CD. Former smokers are also at greater risk than nonsmokers.
• Genetic Factors: Several genetic factors increase the risk for developing CD and having a family member with CD increases the risk of developing the disease. If a person has a relative with the disease, his or her risk is about 10 times greater than that of the general population. If the relative is a brother or sister, the risk is 30 times greater.
  

Changes in diet and lifestyle may help control symptoms
Preventive measures for Crohn’s disease have not been well defined. No specific diet has been shown to improve or worsen bowel inflammation in CD. However, eating a healthy amount of calories, vitamins, and protein is important to avoid malnutrition and weight loss. Foods that worsen diarrhea should be avoided. Each person may have specific foods that seem to worsen or improve symptoms.

The goal of medical treatment is to reduce the inflammation
Currently, there is no medical cure for Crohn’s disease. However, a number of medications have proven effective in helping to control the disease. These include anti-inflammatory and immunosuppressive drugs, immunomodulators and antibiotics.

Biologic therapy is now approved to induce remission in CD patients who have not responded adequately to conventional therapy and also as a long term therapy with or without corticosteroids to maintain remission. Biologic therapy is based on infusion of a monoclonal antibody (infliximab) that blocks the immune system’s production of tumor necrosis factor-alpha (TNF-alpha), a mediator that strongly enhanches inflammation.

There is an increased risk of colon cancer associated with Crohn’s disease, in particular if the disease manifests in the colon. CD patients therefore undergo colonoscopy for routine surveillance of the colon and thus colon cancer is usually detected earlier than among the general population.

Gallstones

The gallbladder is a small, pear-shaped organ located below the liver. Its primary purpose is to store and deposit gall (also called bile), a digestive liquid produced by the liver. After a meal, the gallbladder contracts and sends the bile into the intestine, where it helps with digestion, mainly of fats. When a meal has been digested, the gallbladder relaxes and fills up again with bile from the liver.

Under certain conditions substances found in bile crystallize and accumulate to form one or more gallstones in the gallbladder. Gallstones can vary in size from a grain of sand to a large pebble. The cause of gallstones is not completely known, but scientists believe they form when the bile contains too much cholesterol, too much bilirubin, not enough bile salts, or when the gallbladder does not empty completely or often enough.

Most people with gallstones do not experience any symptoms and may never even know they have them. If gallstones move from the gallbladder and lodge in any of the ducts that carry bile from the liver to the small intestine, they can cause intermittent pain in the upper abdomen area, especially after meals. If a gallstone gets stuck in any of these ducts, and blocks them completely, the result can be a so-called gallbladder attack, with severe and sudden pain in the right upper part of the abdomen or upper back.

If any of the bile ducts remain blocked for a significant period of time, severe damage or infection can occur in the gallbladder, liver, or pancreas. Left untreated, this can be fatal. Warning signs of a serious problem are fever, jaundice, and persistent pain.

About 1 in 5 individuals will develop gallstones, which may require medical intervention, during their life. Gallstones are more common in individuals over the age of 60, women during childbearing age, and amongst certain ethnic groups. In addition, being obese or overweight increases the risk of gallstones. Gallstone formation often runs in families. Thus, the risk is doubled if one has a first-degree relative with gallstones. It is therefore not surprising that a genetic association has been found for this condition.

The deCODEme Complete Scan identifies a variant (rs6756629) in the ABCG5/ABCG8 gene region on chromosome 2 and provides an interpretation of the risk for developing gallstones that is associated with this variant in customers of European descent. Risk information for other ethnicities is currently unavailable.

Risk Factors
It is not known why some people develop gallstones and others do not. However, it is known that several factors can affect the risk of gallstone formation and many people who get gallstones have a combination of the following risk factors:

• Sex: Women are twice as likely as men to develop gallstones, especially during pregnancy. Excess estrogen from pregnancy, hormone replacement therapy, and birth control pills appear to increase cholesterol levels in bile and decrease gallbladder movement, which can lead to gallstones.
• Age: Women can develop gallstones at a young age due to increased risk during pregnancies. In general though, people older than age 60 are more likely to develop gallstones than younger people.
• Ethnicity: Native-Americans and Mexican-Americans have been found to have a genetic predisposition to secrete high levels of cholesterol in bile. In fact, these groups have the highest rate of gallstones in the United States, whereas African Americans of both sexes have the lowest incidence of gallstones.
• Family history: Gallstones often run in families, the risk of developing gallstones is doubled if one has a first-degree relative with the condition.
• Weight: Obesity is a major risk factor for gallstones, especially in women. Studies have also shown that being even moderately overweight increases the risk for developing gallstones.
• Rapid weight loss: As the body metabolizes fat during prolonged fasting and rapid weight loss the liver secretes extra cholesterol into bile, which can lead to gallstones. In addition, the gallbladder does not empty properly during ‘crash-diets’.
• Diet: It is not clear how diet contributes to gallstone formation. However, diets which are high in cholesterol and fat, and low in fiber, may increase the risk of developing gallstones.
• Cholesterol-lowering drugs: Drugs that lower cholesterol levels in the blood actually increase the amount of cholesterol secreted into bile. In turn, the risk of gallstones increases.
• Diabetes: People with diabetes often have high levels of fatty acids called triglycerides. These fatty acids may increase the risk of gallstones.
• Other diseases People with severe liver diseases and some blood disorders, such as sickle cell anemia, can develop gallstones due to a higher concentration of bilirubin in their bile.
  

Prevention and Treatment
Although there is no certain prevention for gallstones, many of the risk factors that are associated with diet and being overweight can be modified in order to reduce risk of gallstone formation, such as:

• Maintain a healthy weight. If you are overweight, it is an important health goal in general to lose excess weight gradually, but also important in terms of preventing gallstones. Rapid weight loss followed by weight gain may increase risk for gallstones, especially in women.
• Eat regularly and maintain a balanced diet. Research shows that eating regular meals that contain some fat (which causes the gallbladder to empty) can help prevent gallstones. Eat a balanced diet including plenty of whole grains and fiber, and have regular servings of food that contain calcium (found in green, leafy vegetables and milk products). Limit saturated (animal) fat and foods high in cholesterol.
• Exercise regularly. Studies have shown that increased levels of physical exercise may be an important way to reduce the risk of forming gallstones.
• Estrogen medications. Since estrogen appears to increase cholesterol levels in bile and thereby increase risk of gallstones, women who are at increased risk for gallstones should discuss with their doctors the pros and cons of estrogen therapy such as in hormone replacement therapy, and birth control pills.
  

The so-called “silent-gallstones” (without symptoms) that so many people have without even knowing about them, are likely to remain silent, and no treatment is recommended.

For gallstones with symptoms, there are several treatment approaches available, but surgical removal of the gallbladder (cholecystectomy) remains the most widely used therapy. This is partly because the newer non-surgical treatments are useful in only some gallstone patients, while surgery can be used in virtually all patients. Patients generally do well after surgery and have no difficulty in digesting food, even though the gallbladder’s function is to aid digestion. Surgical options include the standard procedure, called open cholecystectomy, and a newer, less invasive procedure called laparascopic cholecystectomy (keyhole surgery).

Lactose Intolerance

It may surprise you to learn that lactose tolerance (sometimes also called “lactase persistence”, that is the ability of human adults to digest milk products without experiencing the aforementioned symptoms), is unique among mammals and a relatively new trait among humans.

The history of lactose tolerance is fascinating, as it involves a genetic variant that spread within and among human populations due to positive natural selection, because of the survival and reproductive advantages that it conferred on those who carried it.

Lactose is a natural sugar found in milk and most dairy products and is broken down by the enzyme lactase, produced by cells in the digestive tract. At birth, all mammals produce the lactase enzyme and can therefore drink their mother’s milk without experiencing bloating, cramping or diarrhea. After weaning however, mammal infants stop producing lactase and prepare for an adult diet of raw meats, grass or other delicacies!!

Originally, this was also the case for all humans. However, a few thousand years ago a mutation occurred in the lactase gene of one human ancestor that allowed him or her to continue to digest the lactose in dairy products into adulthood. This is why the trait is sometimes called “lactase persistence”. We do not know who this ancestor was, but it is likely that this person lived somewhere in Europe and belonged to a group that kept milk-producing animals.

The continued production of lactase into adulthood turned out to be highly advantageous, probably because it provided a rich and constant source of nutrition and fluid in groups that kept dairy animals. Individuals in such groups that did not carry the mutation seem to have been at a relative disadvantage, particularly at times when dairy products were the only nourishment available. As a result, the underlying mutation quickly spread within Northern Europe and to some other parts of the world and rose, through positive natural selection , to high frequency in many populations that used domesticated animals such as cattle and goats.

Lactose intolerance ranges in frequency from 2-5% in Northern Europe and up to nearly 100% in Asia, South-Africa and Latin-America, with intermediate rates in North-America and North-Africa. An estimated 30 to 50 million American adults are thought to be lactose intolerant.

The deCODEme Complete Scan identifies a variant SNP close to the lactase gene (LCT) on chromosome 2 and gives an interpretation of the associated genetic risk for lactose intolerance.

risk factors

• Age: Lactose intolerance can begin at different times in life. In people of European ancestry, it usually starts to affect children older than 5 years. In African-Americans it can occur as early as age 2. Infants born prematurely may have reduced levels of lactase, since production of this enzyme starts late in the last trimester.
• Ethnicity: Lactose intolerance is highly dependent on ethnicity: 95 percent of Asians, 60 to 80 percent of African Americans and Ashkenazi Jews, 80 to 100 percent of American Indians, and 50 to 80 percent of Hispanics have lactose intolerance. It is least common in people of North-European origin (2-5%).
• Genetics: The ability to digest lactose in adults is inherited as a dominant Mendelian trait. This means that it is caused mainly by your genetic makeup with little or no influence from the environment. A sequence variant (SNP) near the lactase gene has been identified that determines whether people are “lactase persistent” or “lactose intolerant”, that is whether the expression of the gene that controls lactase production is turned on or off during adulthood. This means that your genotype will, with high probability, predict whether you are lactose intolerant or not. Note however, that even if you turn out to have the variant that enables you to digest lactose during adulthood, you could still have other variants that make you sensitive or even allergic to milk. It should also be noted that the variant reported here does not account for every case of lactase persistence, particularly in people that trace their ancestry to sub-Saharan Africa. In this part of the world it is thought that other, presently unidentified, variants are also responsible for cases of lactase persistence.

Prevention
Being lactose intolerant or lactase persistent during adulthood depends completely on your body’s ability to produce lactase, which is genetically determined. There is no scientific evidence to indicate that diet or lifestyle has an impact on your ability to produce lactase as an adult. For example, avoiding milk completely for long periods does not lead to a change in lactase production.

However, removing milk products from the diet usually improves the symptoms of lactose intolerance. Milk products that are soured or otherwise treated (like yogurts and solid cheeses) contain relatively low levels of lactose and the soured products may even contain the lactase-producing Lactobacillus Acidophilus. As a result, these milk products cause fewer problems for lactose intolerant people compared to other milk products. Lactose intolerant people who avoid milk products should supplement their diet with calcium-rich food and vitamin D to build up and maintain a healthy bone mass.

Note that having lactose intolerance is not the same as being allergic to milk. Unlike an allergy, lactose intolerance does not involve your immune system and does not necessarily mean that you will have to completely avoid dairy products.

Obesity

Obesity, defined by the World Health Organization as a body mass index (BMI) greater than 30 kg/m², is an ever increasing problem in most regions of the world.

It is estimated that there were more than 400 million obese individuals over the age of 15 worldwide in 2005 and this number is projected to rise to over 700 million by 2015. The prevalence of obesity among adults in the US is 32.2% and in 2005 the number of obesity -related deaths was calculated to be over 100,000 per year. Overweight and obesity among American children (ages 6-19 years) has risen dramatically in the last decade, with a prevalence of more than 17%. The prevalence of adult obesity in Europe varies by country, but is as high as 20% for men and 30% for women.

Adult obesity is a major risk factor for several conditions such as cardiovascular disease, type 2 diabetes, abnormal blood cholesterol, high blood pressure, osteoarthritis, and some forms of cancer. The associated co-morbidities of childhood obesity are no less serious than in the adult form and include related conditions of the aforementioned adult complications as well as early puberty, orthopedic problems, and various psychological symptoms. Furthermore, individuals who are obese as children are more likely to be obese as adults, especially if one or both parents are also obese.

Obesity is known to run in families, but despite considerable efforts, mainly rare genetic variants have been identified that increase the risk of becoming obese. However, our scientists at deCODE genetics and others have recently discovered new variants, bringing the total to 11 variants in 11 regions of the genome, that increase an individual’s risk of being obese.

The deCODEme Complete Scan identifies the above mentioned variants and provides interpretation of their associated risk for becoming obese in customers of European descent. Information regarding the association between obesity and the above mentioned variants in other ethnicities is currently unavailable.

risk factors
Risk factors for developing obesity include:

• Childhood obesity: Obesity in children and adolescents often continues into adulthood.
• Being overweight: Overweight is defined as a body mass index (BMI) greater than 25 kg/m² but less than 30 kg/m². Being overweight can eventually lead to obesity.
• Excessive caloric intake: Increased caloric intake, especially in the form of saturated fats and simple sugars, increases the risk of becoming obese.
• Sedentary lifestyle: A sedentary lifestyle and general lack of physical activity increases the likelihood of becoming obese.
• Ethnicity: Hispanic and African Americans are at greatest risk, followed by individuals of European and Asian descent.
• Genetics: Twin and adoption studies have shown that genetic factors play an important role in obesity. Large groups of individuals have been evaluated for genetic variation related to the development of obesity. The genetic variations identified can be divided into 2 main groups:

1) rare forms that explain only a small fraction of the obese population, and
2) common forms that are present in a larger proportion of the obese population, such as the ones presented here.

Prevention and treatment
Obesity is the second leading preventable cause of death after smoking. Obesity is mainly caused by consuming more calories than are used during physical activity and daily life. General prevention involves balancing dietary intake and physical activity to maintain a healthy body weight.

Treatment for obesity includes restricted caloric intake and an exercise program. Both should be structured towards permanent change in lifestyle and long-term maintenance of an appropriate weight. An obesity treatment regimen may include behavioral management (such as goal setting and support groups), medications, and, in some cases, surgery. Everyone intending to make significant changes in their diet or lifestyle should first seek advice from their doctor. Treatment of obesity is a crucial health issue because it is associated with many other serious diseases.

Type 1 Diabetes

Type 1 Diabetes is one of the most common chronic diseases in childhood and adolescence. About 1 in every 400 to 600 children and adolescents develops T1D, and more than 700,000 Americans are currently living with T1D (0.4% of the population). The number of new cases of T1D in the US has been increasing by approximately 3% per year.

T1D is an autoimmune disease that can occur at any age, but it usually develops before age 30. In this type of diabetes, the islet cells of the pancreas are attacked and destroyed by the immune system. The islet cells normally produce insulin, the hormone that moves sugar from the bloodstream into the body’s cells and tissues, where it can be used for energy. When the islet cells are destroyed, little to no insulin is produced, which means that sugar cannot be moved out of the blood and blood sugar levels rise. Individuals with T1D have an increased risk of developing several serious health complications, including cardiovascular disease, kidney failure, and blindness.

The etiology of T1D is largely unknown but it has been shown that genetic factors are important risk factors. Genetic variants in 11 different genes have been identified that increase the risk of developing T1D; in the HLA-DRB1 gene on chromosome 6, the PTPN22 gene on chromosome 1, the IL-2RA gene on chromosome 10, the PTPN2 gene on chromosome 18, the ERBB3 and the C12orf30 genes on chromosome 12, the IFIH1 gene on chromosome 2, the KIAA0350 gene on chromosome 16, the INS gene on chromosome 11, the IL21 gene on chromosome 4 and the CTLA4 gene on chromosome 2.

The deCODEme Complete Scan identifies variants in the 11 genes listed above and provides interpretation of their associated risk for the development of T1D in customers of European descent. Currently no data are available for people of other ethnicities for the variants listed above.

risk factors
The causes for T1D are unclear, but genetic and/or environmental causes that trigger the autoimmune destruction of insulin-secreting islet cells in the pancreas seem to be the main players.

• Ethnicity: People of European decent have a greater risk of developing T1D than African Americans, Asians, or Hispanics.
• Genetics: A large body of evidence indicates that genetic factors influence both the risk of developing T1D and the resistance to developing T1D. T1D tends to run in families, with an average 6% risk of two siblings developing the disease compared with a 0.4% risk of two unrelated individuals developing the disease.
  

Prevention and treatment
There is no known way to prevent T1D, though several clinical trials are underway or being planned to investigate methods for preventing or slowing down the disease.

There are certain steps that can be taken to lower the impact of T1D on health and quality of life by reducing the risk of developing serious medical complications associated with diabetes. The sooner T1D is detected and treatment can begin the better. At this time, the medical community has no established procedure for screening at-risk children. If a child’s close family member (parent or sibling) has T1D, that child should be monitored for symptoms (such as unusual thirst or hunger and increased frequency of urination).

T1D is treated with blood sugar monitoring, insulin, exercise, and a special diet. Untreated T1D is life threatening. To survive, people with T1D must have insulin delivered several times a day by injection or a pump. Without proper daily management of blood sugar levels, medical emergencies and serious health complications may arise that may decrease quality of life and length of life.

Type 2 Diabetes

Type 2 diabetes (T2D) (also called non-insulin dependent diabetes mellitus or adult-onset diabetes) is the most common form of diabetes. In T2D, the body does not respond well to insulin, a hormone that helps transfer sugar out of the blood and into the body's cells and tissues, where it is used for energy.

At first, the islet cells in the pancreas try to produce more insulin in an effort to make the body respond. But eventually, these cells cannot keep up and stop working altogether, so sugar stays in the blood. People with T2D have difficulty maintaining normal blood sugar levels.

If blood sugar levels are not controlled, T2D can lead to the development of several life-threatening complications such as heart disease, stroke, hypertension, and kidney failure. Patients with T2D also develop blood circulation problems that can lead to blindness and even amputation of extremities in extreme cases.

It is estimated that a total of 20.8 million people, or 7% of the US population, were living with diabetes in 2005. Of those, an estimated 6 million were undiagnosed. Currently, over 1.5 million people are diagnosed with diabetes in the US each year, and the number of new cases of T2D is steadily increasing due to the growing number of older Americans, increasing obesity, and lack of exercise.

An increasing number of genetic variants have been consistently found to contribute to the risk of developing T2D. Variants in the TCF7L2 gene appear to be associated with the highest risk of developing T2D, and also can predict the likelihood that a person will convert from a state of pre-diabetes (borderline blood sugar levels) to full-blown T2D. Several studies have shown that overweight pre-diabetics who have certain TCF7L2 variants have a 55-70% chance to develop T2D within 3 to 5 years after their initial diagnosis. It has been shown by the NIH-sponsored Diabetes Prevention Program Outcome study that weight loss and treatment with metformin can prevent or delay the transition from pre-diabetes to T2D in this high-risk group.

The deCODEme Complete Scan identifies variants in or near 15 genes, including the TCF7L2 gene, and provides interpretation of their associated risk for the development of T2D. At this time we provide this information on all variants for individuals of European descent. Information for 8 out of the 15 variants is provided for East Asians. For African Americans we provide information on TCF7L2, the individually strongest genetic risk factor.

risk factors

• Overweight or obesity: Type 2 diabetes (T2D) is associated with obesity and resistance to the effects of insulin. Most people with the disease are overweight at the time of diagnosis, and they are more likely to have central obesity (fat concentrated around the waist). T2D can develop in those who are thin, especially the elderly.
• Age: Most patients are over the age of 45 at the time of diagnosis, but a growing number of children and adolescents are being diagnosed with T2D, most likely due to the rise in childhood obesity.
• Abnormal cholesterol levels: People with T2D often have high total cholesterol combined with low HDL cholesterol (less than 35 mg/dL) and high triglyceride levels (over 250 mg/dL).
• Other cardiovascular disease risk factors: High blood pressure, a history of heart disease, and lack of physical activity are also common risk factors for developing T2D.
• History of gestational diabetes: Women who develop diabetes during pregnancy are at higher risk of developing T2D later on in life.
• Ethnicity: Compared with Individuals of European origin, African-Americans, Hispanic/Latino Americans, American Indians, some Asian Americans, and Native Hawaiians or other Pacific Islanders, are at a higher risk for T2D and its complications.
• Genetics: Having a family history of T2D is associated with increased risk for developing the disease. Variants in the TCF7L2 gene appear to be associated with the highest risk of developing T2D, and also can predict the likelihood that a person will convert from a state of pre-diabetes (borderline blood sugar levels) to full-blown T2D. Several studies have shown that overweight pre-diabetics who have certain TCF7L2 variants have a 55-70% chance to develop T2D within 3 to 5 years after their initial diagnosis.
  

Prevention and treatment
To prevent the development of Type 2 Diabetes (T2D), it is generally recommended that people maintain a normal body weight. Studies show that people at high risk for T2D can prevent or delay the onset of the disease by losing 5 to 7 percent of their body weight. Also shown by the NIH-sponsored Diabetes Prevention Program Outcome study is that for a certain group of high-risk individuals (overweight, pre-diabetic individuals with certain TCF7L2 variants), weight loss and treatment with metformin can prevent or delay the transition from pre-diabetes to T2D.

In general, following a healthy lifestyle, which includes maintaining a healthy weight, exercising (getting at least 30 minutes of physical activity 5 days a week), having a modest dietary fat intake, and eating a good amount of fiber and whole grains, can reduce the risk of T2D.

Even if T2D has already been diagnosed, these changes in lifestyle are recommended to control blood sugar as much as possible and decrease the risk of developing other health problems associated with T2D, such as heart disease. When diet and exercise do not help maintain normal or near-normal blood sugar levels, doctors can prescribe medications or daily insulin injections.

Ulcerative Colitis

Ulcerative colitis is an inflammatory condition of the colon
Ulcerative colitis belongs to a group of diseases known as inflammatory bowel diseases (IBD), or diseases that cause inflammation in the digestive tract. In ulcerative colitis, small ulcers develop in areas where inflammation has damaged or killed the cells lining the colon. These ulcers usually become infected, which along with the bleeding, causes the colon to empty frequently, resulting in cramping abdominal pain and diarrhea.

Ulcerative colitis affects the innermost lining of colon or rectum
Ulcerative colitis is related to another type of IBD called Crohn's disease. The two diseases differ mainly in the depth of the inflammation and location within the digestive tract. Whereas ulcerative colitis affects the colon mucosa, the innermost lining of the colon and rectum, Crohn's disease causes inflammation deeper within the intestinal wall and occurs in other parts of the digestive system, including the small intestine, mouth, esophagus, and stomach.

A chronic disease with symptoms that can come and go
Symptoms of ulcerative colitis and its complications, vary depending on the extent of inflammation in the rectum and colon. About half of those diagnosed with ulcerative colitis continue to have mild symptoms that come and go, whereas others may experience chronic debilitating symptoms leading to life-threatening complications. Even those with a severe form of the disease may have relatively symptom-free periods between flare-ups.

Mostly diagnosed in young people of European origin
Ulcerative colitis can occur in people of any age, but the disease is usually first diagnosed in people in their 30s. It is more frequently diagnosed in individuals of European origin and in those of Jewish descent and affects men and women equally.

Genetics are one of the few known risk factors
The direct causes of ulcerative colitis are unknown. Those diagnosed with the disease often also have disorders of the immune system, but it is not known whether they are a cause, a result, or simply a correlate of ulcerative colitis. Genetic factors are known to play a significant role in the development of the disease. Up to 20% of people diagnosed have a close relative with ulcerative colitis or Crohn's disease.

deCODEme can calculate your genetic risk of ulcerative colitis
Nine genetic variants, on chromosomes 1, 3, 6, 10, 12 and 18 have been associated with increased risk of developing ulcerative colitis. Of these, four variants, on chromosomes 1, 3, 10 and 18, have also been associated with increased risk of developing Crohn's disease.

The deCODEme Complete Scan identifies all nine variants and provides an interpretation of the associated risk of ulcerative colitis for individuals of European descent. At the current time, risk information for other ethnicities is not available for these variants.

Risk Factors
Although the direct causes of ulcerative colitis are not known, certain factors have been found to be associated with higher risk of developing this disease:

• Age. Ulcerative colitis can develop at any age, but is most often diagnosed in people in their 30s. However, some may not develop the disease until after 50 or 60 years of age.
• Ethnicity. Ulcerative colitis is most common among people of European descent. People of African descent have a lower incidence, as do individuals who originate from Asia and South America. Jewish people have been found to have the highest risk of developing ulcerative colitis.
• Family history is currently the most prominent risk factor. Genetics have been found to play a significant role in the development of the disease, with reports of up to 20% of people diagnosed with ulcerative colitis having a first-degree relative with ulcerative colitis or Crohn's disease.
• Environmental factors. People living in northern latitudes and in urban areas of industrialized countries, seem to be at a higher risk of developing ulcerative colitis. Other environmental factors, such as a diet high in fat or refined foods, may also play a role.
• Inflamed bile ducts due to a condition called primary sclerosing cholangitis, have been found to be associated with ulcerative colitis.
• Left-Handedness. Curiously, people who are left-handed are reported to have a higher risk for both ulcerative colitis and Crohn's disease.
  

Prevention and treatment
Since the causes of ulcerative colitis are unknown, not much is known about how to prevent the disease. However, some studies have found that women who breastfeed their children are at lower risk than those who do not, and that smokers have a lower than average rate of ulcerative colitis (while they have a higher than average rate of Crohn's disease). This association most certainly should not encourage people to smoke, but raises interesting questions about the possible role of nicotine in the inflammatory processes of these bowel diseases.

Treatment for ulcerative colitis depends on the severity of the disease. It usually includes medications to reduce the inflammation, fight infections, and control pain, along with changes in diet to maintain adequate nutrition and prevent or reduce diarrhea.

Surgery may become necessary if the disease does not respond to medications or if complications arise. Surgery may also be considered sooner than later to prevent the development of colorectal cancer, which has been found to be associated with a long history of active ulcerative colitis.

Complications of ulcerative colitis that require urgent surgery include perforation of the colon, increased bleeding, and a condition called toxic megacolon, in which the muscle wall of the colon dilates and bacteria and gases build up inside the colon.

The most common surgical procedure for ulcerative colitis is proctocolectomy (removal of the entire colon and rectum). Unlike Crohn's disease, which can recur after surgery, ulcerative colitis is “cured” once the colon is removed.

Male Pattern Baldness

Male pattern baldness (androgenic alopecia) is the most common form of hair loss in men. Men affected by this condition lose their hair in a well-defined pattern, beginning above both temples.

Over time, the hairline recedes to form a characteristic "M" shape and existing hair may become finer and shorter. Hair also thins at the crown of the head, often progressing to partial baldness (forming a horseshoe pattern of hair around the sides of the head) or in some to complete baldness (see figure).

Some degree of male pattern baldness affects roughly 50% of males of European descent during their lifetime. The proportion of affected males increases steadily with age. The incidence and the effects of male pattern baldness tend to be greatest in men of European ancestry, second highest in Asians and African Americans, and lowest in Native Americans and Eskimos.

Male pattern baldness is, in part, a genetically determined condition, associated with a genetic variant in the Androgen Receptor (AR) gene on the X chromosome , one of the so-called sex-chromosomes. Males have one X chromosome and one Y chromosome whereas females have two X chromosomes. Since sons always inherit their X chromosome from their mothers, the genetic variant in the AR gene associated with male pattern baldness is inherited maternally.

The deCODEme Complete Scan identifies a sequence variant (rs2223841) in the AR gene on chromosome X and provides an interpretation of the associated genetic risk for male pattern baldness in men. Current research has not provided the data to support an interpretation of the associated risk for hair loss in women for this variant.

prevention
Male pattern baldness does not indicate a medical disorder. There is no known prevention for male pattern baldness and treatment is not necessary, unless people are uncomfortable with their appearance. Hair weaving, hairpieces, or change of hairstyle may disguise the hair loss. This is usually the least expensive and safest approach for hair-thinning and baldness. Hair loss is usually permanent, but there are medications available that can slow the hair-thinning process:

Minoxidil – a solution applied directly to the scalp to stimulate the hair follicles and slow hair loss. It is most effective for people under 40 years of age whose hair loss is recent and has no effect on receding hairlines. The previous degree of hair loss returns when applications are stopped. Minoxidil is the only medication approved for hair loss in women.

Finasteride – a prescription pill that is used alone or in combination with other medications to treat benign enlargement of the male prostate gland. Like minoxidil, the results are more likely to be slower hair loss than actual new hair growth. The previous degree of hair loss returns when people stop taking the drug.

Psoriasis

Psoriasis is a chronic inflammotory skin disease
Psoriasis is a chronic inflammatory disorder of the skin, the body’s largest organ and the first line of protection from the environment. Although the direct cause of psoriasis is currently unknown, it results in skin cells growing abnormally fast, causing the skin to shed every three to four days.

An autoimmune disease
There are five types of psoriasis: plaque, guttate, inverse, pustular and erythrodermic. The most common form, plaque psoriasis, is characterized by inflamed, scaly, red, itchy patches called psoriatic plaques. It is a fluctuating condition with recurrent episodes of variable severity. About 10% to 20% of psoriasis patients develop psoriatic arthritis, an inflammatory joint disease.

Psoriasis and psoriatic arthritis are considered to be autoimmune diseases, in which the immune system attacks the body’s own tissues.

Most common among people of European ancestry
Psoriasis is most common among people of European ancestry (with a prevalence of 2% to 3%). Women have a slightly higher risk of developing psoriasis according to some studies. Psoriasis is estimated to affect 5 to 7 million people in the US.

Genetics contribute to the development of Psoriasis
There are eight genetic variants known to increase the risk of developing psoriasis; located on chromosomes 1, 5, 6, and 12. Of these the variant in the HLA-C gene contributes by far the strongest effect to the risk of developing psoriasis in most if not all populations tested.

deCODEme can calculate your genetic risk
The deCODEme Complete Scan identifies the eight genetic variants listed above and provides interpretation of their associated risk for developing psoriasis in individuals of European descent.

In East Asians, the deCODEme Complete Scan currently calculates genetic risk associated with three variants; on chromosomes 1, 5, and the HLA-C variant on chromosome 6. Currently no risk data are available for people of other ethnicities for the variants listed above.

Risk factors
Family history is the greatest risk factor
A family history of psoriasis is the greatest risk factor. In a study of identical twins, 70% of twins who had psoriasis had a twin who also had psoriasis. Studying identical twins for concordance (both twins having the same disease) is generally a good measure of genetic contribution since their inherited genetic material (DNA) is identical. A 70% concordance rate is considered to be very high for a condition of complex inheritance such as psoriasis.

A genetic connection exists between psoriasis and the immune system
Psoriasis appears to involve the immune system. Therefore, it is not surprising that the gene most strongly and consistently associated with psoriasis is a gene important in immune response. HLA-C, specifically HLA-Cw6, is associated with psoriasis in most, if not all, populations tested. Commonly, over 60% of psoriasis patients carry one or more copies of the Cw6 variant of HLA-C compared with 8% to 12% of those who do not have psoriasis.

On average, psoriasis patients who have the Cw6 variant tend to develop the disease a few years earlier and can have more severe progression of the disease compared with psoriasis patients who do not have the Cw6 variant. Recently, two other genes, IL-12beta and IL-23R, have been associated with psoriasis, but they do not seem to play as important a role as HLA-Cw6 in their contribution to the risk of developing the disease.

Prevention and treatment
Psoriasis is not contagious. No preventive measures are known to be effective, since not much is known about what triggers the onset of psoriasis. Usually, no obvious trigger is found. Some studies have indicated that an infection (most often a streptococcal infection or "strep throat") can stimulate or perhaps over-stimulate the immune system into a state of self-attack. Several other factors including smoking, excessive drinking, and stress are known to worsen or exacerbate symptoms.

Effective treatments are available
At the present time, there is no cure for psoriasis. There are many treatments available depending on disease severity, ranging from skin moisturizers to immunosuppressive medications. The goal of treatment is to reduce inflammation and slow the rapid growth and shedding of skin cells.

Courtesy: deCODEme, The American Cancer Society , National Cancer Institute , MayoClinic.com , MedlinePlus. Please visit the website for further information