1. Assesses type 2 diabetes risk
deCODE T2™ is test that measures four DNA markers which are widely replicated genetic risk factors for type 2 diabetes (T2D). It defines genetic risk for T2D, independent of family history and obesity, that ranges from 0.6 to 2.2 fold the general population risk.
deCODE T2™, like other DNA based tests for common disease, is a risk assessment test as it measures DNA risk markers that are not determinative but associate with the disease in certain proportion of the patients. Patients with higher genetic risk are not destined to develop T2D and conversely, patients with lower genetic risk are not immune from diabetes. There are other risk factors not measured by the deCODE T2™ test. DNA markers for common disease simply are risk markers comparable to biomarkers such as LDL-cholesterol and PSA that predict risk for cardiovascular diseases and prostate cancer respectively.
By knowing and understanding genetic risk, it may be possible to take actions that reduce or minimize the likelihood of an individuals developing diabetes. In addition to predicting or recalculating the remaining lifetime risk of developing T2D, the deCODE T2™ results can predict the likelihood of prediabetes converting to full blown T2D and which patients may benefit the most from preventive management.


2. Assesses risk for the prediabetic pateints
deCODE T2™ offers new means to help physicians decide which prediabetic patients are at 50 to 70% absolute risk for converting T2D within 3 to 4 years compared to the baseline risk of 30% in overweight or obese prediabetics. These high-risk patients therefore may benefit the most from more aggressive management either through lifestyle modification or drug treatment. The 2008 ADA recommendations on management of prediabetics state: “In addition to lifestyle counseling, metformin may be considered in those who are at very high risk (combined IFG and IGT plus other risk factors) and who are obese and under 60 years of age.” deCODE T2™ is one of the strongest risk factors for conversion.
Prediabetic patients with higher genetic risk for T2D, may be more compliant with weight loss recommendations by their physicians. For patients who fail to lose significant weight within 6 months, high risk prediabetics may benefit the most from nutritional advice and more aggressive lifestyle intervention. Finally, high risk prediabetics who still fail to respond to lifestyle intervention, would be prime candidates for metformin as suggested by the latest ADA recommendations.


3. Identify type 2 diabetics who respond poorly to sulfonylurea
Regarding patients who already have T2D studies in two populations show that those who have two copies of the risk variant at TCF7L2, one of the genes included in deCODE T2™, have much lower response to sulfonylurea, with only 36% meeting HbA1C target of 7% or lower, versus 62% of those who do not have two copies (Pearson, E.R., et al., Diabetes, 2007. 56(8): p. 2178-82 and American Diabetes Association 67th Scientific Sessions, 2007). Metformin response on the other hand did not depend on the TCF7L2 genotype, meaning that patients who have the high-risk TCF7L2 genotype are likely to respond better to metformin than sulfonylureas.

Genetic Markers
The DNA markers included in deCODE T2™ are located in or near the following genes: TCF7L2, PPARG, CDKAL1, and CDKN2A and have each been widely replicated in 10 to 40 independent populations. TCF7L2 is the strongest genetic risk factor discovered so far for Type 2 diabetes and has been validated in over 40 populations spanning several ethnicities. The TCF7L2 marker correlates with lower insulin secretion in response to oral glucose. deCODE T2™ combines the risk due to TCF7L2 with the three other widely validated genes. The T2 genetic profile derived for each patient is based on a reference set of tens of thousands of patients and controls. This genetic profile defines risk ranges from 0.6 to 2.2 compared to the risk in the general population. About 40 % of the population has a genotype combination of the tested markers that have an increased relative risk (>1) over the general population, about 8% of the population have 1.5 to 2.2 relative risk, about 3% of the population have genotype combinations that confer a 1.8 to 2.2 fold relative risk.
The deCODE T2™ genetic risk profile is independent of other risk factors for type 2 diabetes such as family history, obesity, prediabetes, and ethnicity. The genetic risk can be multiplied by the other risk factors not measured by this test to derive a composite risk relative to that in the general population. Therefore, this test is useful for patients with or without family history of T2D.

1. TCF7L2
The TCF7L2 gene is by far the strongest genetic risk factor discovered so far for Type 2 diabetes and is responsible at the population level for more T2D cases than all the other identified variants combined. Since deCODE’s publication in 2006 (Grant, S.F., et al., Nat Genet, 2006. 38(3): p. 320-3) about 40 independent studies around the globe have validated its association to T2D. About 8 - 11% of the general population (of European or African descent) carry two copies of the risk variant, compared to about twice that number of type 2 diabetics. The frequencies are lower in Asian and Hispanic populations but the relative risk is the same.
Having two copies of the risk variant has been shown to correspond to an approximate doubling of the likelihood of developing T2D compared to the most common genotype (no copies). (Remember that we all have two copies of each chromosome in every cell in our bodies. We inherit one copy from our mother, and one from our father.) The risk variant is the T allele of SNP rs7903146, located within the transcription factor 7-like 2 (TCF7L2) gene.
A published U.S. government supported clinical trial involving thousands of overweight and obese prediabetics, the Diabetes Prevention Program, and a European study, the Diabetes Prevention Study, showed that prediabetics with two copies of the risk variant were at a 1.8 to 2 times greater risk of progressing to type 2 diabetes within the next three to four years as were prediabetics with one or no copies of the risk variant (that is a 50 to 70% absolute risk to convert compared to a baseline conversion rate of 30 to 35% for overweight and obese prediabetics). Approximately 20% of prediabetics who went on to develop T2D in these studies carried two copies of the risk variant compared to 11% of study participants overall.
Importantly, this study also showed that this increased risk could be effectively reduced through weight loss and treatment with metformin. Furthermore, the 2008 ADA guidelines : “In addition to lifestyle counseling, metformin may be considered in those who are at very high risk (combined IFG and IGT plus other risk factors) and who are obese and under 60 years of age.”
Increased genetic risk results according to deCODE T2™, including TCF7L2 is one of the strongest risk factors for conversion.


2. CDKAL1
deCODE genetic has recently shown that a sequence variant in the CDKAL1 gene can increase the risk of developing type 2 diabetes by about 30%. (Steinthorsdottir, V et al. Nat Genet. 2007; 39:770-5). The function of the CDKAL1 gene is unknown but it is expressed in the insulin secreting pancreatic beta cells. Furthermore, this variant affects pancreatic beta cell function as carriers secrete less insulin in response to glucose than those who do not carry the variant.

3. PPARG
A large number of studies have shown that a sequence variant in the PPARG gene affects the risk of developing type 2 diabetes (Deeb, SS et al. Nat Genet. 1998; 20:284-287; Altshuler, D et al. Nat Genet. 2000; 26:76-80; Saxena, R et al Science 2007; 316:1331-6; Zeggini, E et al Science 2007; 316:1336-41; Scott, LJ et al. Science 2007; 316:1341-5). This variant is termed Pro12Ala as it changes a proline in position 12 in one isoform of the protein to an alanine. The common proline variant is thought possibly to confer increased risk of T2D through a decrease in insulin sensitivity. A meta-analysis of three large studies, including a total of 14,586 cases and 17,968 control individuals of European decent, shows that each copy of the major allele of this variant carries with it a 1.14 fold increase in risk of developing T2D compared to those who do not carry the variant. (Altshuler, D et al. Nat Genet. 2000; 26:76-80). Even though the PPAR gamma protein is a receptor for thiazolidinediones (class of T2D drugs), current evidence to suggest that the Pro12Ala variant has no effect on the therapeutic efficacy of this class of drugs.


4. CDKN2A
A sequence variant on chromosome 9p21 was recently shown to confer risk of type 2 diabetes with a relative risk of 1.06 compared to the general population (Saxena, R et al Science 2007; 316:1331-6; Zeggini, E et al Science 2007; 316:1336-41; Scott, LJ et al. Science 2007; 316:1341-5). There are no genes overlapping this variant but the nearest genes are CDKN2A and CDKN2B. It is not known if the sequence variant exerts its effect on type 2 diabetes through these genes or through some other unknown mechanism.

Explanation of risk assessment
The deCODE T2™ genetic risk profile reported for your patient is simply the risk of each DNA marker multiplied by each other and ranges from 0.6 to 2.2 fold. This is justified based on large studies which showed that each genetic marker is an independent risk factor for T2D.
The remaining lifetime risk is defined as the risk to develop T2D after a certain age, assuming the patient has not already been diagnosed with T2D. It is dependent on known risk factors, such as obesity, ethnicity, family history, prediabetes, and age. The genetic risk identified by the deCODE T2™ test is largely independent of any other risk factors that the patient may have and therefore may be multiplied by the relative risks conferred by them.
The remaining lifetime risk for an individual (see table below) can be multiplied by the combined genetic risk identified by deCODE T2™ profile to obtain his/her specific residual lifetime risk. For example, for an overweight white male who is 45 years of age, the remaining lifetime risk according to the table is 23.7%. If his identified deCODE T2™ is 1.8 his remaining lifetime risk has increased to 42.6% However, not all genetic risk factors are known or measured by deCODE T2™ but deCODE T2 measures the strongest known and validated markers.

Remaining lifetime risk by age, BMI, race and sex (modified from Naryan et al. JAMA. 2003 Oct 8;290(14):1884-90)

The deCODE T2™ may therefore provide a new means to help physicians to decide which prediabetics they wish to treat more aggressively either through lifestyle change or through drug treatment. Published studies have shown that certain medications do appear to effectively slow the rate of progression from prediabetes to T2D. The 2002 Diabetes Prevention Program study showed that metformin could decrease conversion by 31% overall and even higher in patients younger than 60 ( N Engl J Med 346, op. cit.). Recent ADA guidelines state: “In addition to lifestyle counseling, metformin may be considered in those who are at very high risk (combined IFG and IGT plus other risk factors) and who are obese and under 60 years of age”

deCODE AF™ is a DNA-based test aimed at detecting Atrial Fibrillation (AF) and subsequently choose the appropriate follow up treatment.
deCODE AF™ detects versions of two common single-letter variations in the genome (also known as SNPs) on chromosome 4q25 that deCODE has identified as major risk factors for atrial fibrillation (AF). deCODE discovered these genetic markers and has published them in a peer-reviewed journal (Nature 2007: Variants conferring risk of atrial fibrillation on chromosome 4q25).
The article can be found under "Letters" in Nature's "Advance online publication".
AF is the most common type of cardiac arrhythmia, or irregular heart rhythm, and is the leading cause of cardiogenic stroke. Between 15 and 20 percent of all strokes are cardiogenic, the subtype with the highest morbidity and mortality.
By providing a better understanding of an individual’s risk, deCODE AF™ may enable doctors to identify those patients who may benefit from outpatient cardiac monitoring for undiagnosed AF. Published research and best clinical practice suggest that individuals with AF, and with a history of stroke or with other risk factors, can significantly reduce their risk of stroke through treatment with the anticoagulant drug, warfarin.

Some stroke patients have intermittent AF and may no longer be in AF when they arrive at an emergency room. Many of these may not be diagnosed during the standard 24 to 48 hours of inpatient cardiac monitoring. As a result, these patients may be placed on an antiplatelet agent rather than much more effective warfarin treatment for secondary prevention of AF-related stroke. More extensive outpatient cardiac monitoring is not routinely done due to the expense involved. deCODE AF™ offers a novel means of meeting this challenge – of identifying those who may benefit from outpatient cardiac monitoring after leaving the hospital, and thereby detecting a greater proportion of AF cases .

deCODE AF™ can only be ordered with the written informed consent of the individual to be tested accompanied by the authorization of a physician. Because deCODE believes this test is useful for informing monitoring and treatment strategies for those who have suffered either ischemic stroke or transient ischemic attack, we recommend that physicians read through this site and the information it contains and then review it fully with their patients, in order to explain what atrial fibrillation is and why the information yielded by the risk test may, together with analysis of other risk factors, be useful for providing the best possible prevention strategy for future stroke.

Genetic Markers
The key to developing a clinically useful DNA-based test for risk of atrial fibrillation (AF) is the identification of common genetic variants that confer significantly increased risk of the condition. deCODE AF™ detects the first two SNPs that meet this criteria and that have been shown to confer risk in multiple populations.
To identify genetic variants conferring risk of AF in the general population, deCODE conducted a genome-wide analysis of more than 300,000 SNPs across the entire genome in a cohort of a total of 5,000 Icelandic AF patients and healthy controls. Alleles (bases) of two SNPs, rs2200733 and rs100233464, both located near the PITX2 gene on chromosome 4q25, were found to be significantly more common in AF patients than in control subjects. The PITX2 gene is known to play a role in cardiac development.
These findings were then validated in studies of a total of more than 18,000 patients with all forms of AF and controls, including cohorts from Iceland, Sweden, the Massachusetts General Hospital in Boston, and, for the strongest of the variants, a cohort of Han Chinese from Hong Kong. The deCODE AF test measures the at-risk versions of these two SNPs. Approximately 30% of those of European ancestry in deCODE’s studies are positive for the deCODE AF™ test, corresponding to an average 2-fold increase in likelihood of AF compared to those negative for the test.

Risk assessment
Stroke is a leading cause of disability and death, and its burden on the healthcare system is increasing with the aging of the population. Atrial fibrillation (AF) is the leading cause of cardiogenic stroke, the subtype of the disease with the highest morbidity and mortality. It has been shown that treatment with warfarin can reduce the risk of stroke in those with AF by about 70%.
Two studies have shown that an extra week of ambulatory cardiac monitoring using an automated digital event recorder following a stroke may identify AF in another 5.6 to 14.3% of stroke survivors. These include many who would originally be given the diagnosis of stroke of unknown etiology as well as carotid atherosclerosis-related stroke. Monitoring all ischemic stroke patients in an ambulatory setting is often considered too expensive roughly one-third of post-stroke and post-TIA patients are at hight risk for atrial fibrillation, especially when the etiology is not clear deCODE AF™ may identify patients who have intermittent AF and who are thus at high risk of recurrent stroke. Warfarin treatment of these cases may decrease the future costs of morbidity and mortality that more than outweighs the extra cost of testing and monitoring.
With the widespread current use of statins, the incidence of myocardial infarction is slowly decreasing. By contrast, the rate of stroke is increasing as a higher proportion of the population survives to the age of higher risk of stroke. It is also clear that statins have only about half the effect on stroke prevention as they do on MI prevention. Part of this may be because much of AF is not related to atherosclerosis. Therefore, we may expect the proportion of stroke due to diagnosed and undiagnosed AF to continue to increase as the atherosclerosis-related strokes are decreased by statins and anti-platelet agents. In order to effectively address AF-related strokes, a test such as deCODE AF™ may improve AF detection which can enable physicians to personalize the treatment of those with AF, delivering the benefits of warfarin to those who need it.

The deCODE BreastCancer™ test determines whether the subject has inherited the risk or non-risk version at 7 different variable sites in the human genome. By comparing deCODE BreastCancer™ test results to the general risk of women in the population it can be seen whether the person tested has a risk greater or lower than the average population risk. The risks at each of the 7 markers are multiplied together to define combined risks from 0.4-to 4.0- fold the relative general population risk. The deCODE BreastCancerTM test examines only genetic risk factors, so other factors such as age and hormonal factors need also to be taken into account. By combining the test results and risks associated with other known risk factors, a more complete lifetime risk estimate can be generated.

The test is done on the DNA isolated from an inner cheek or a blood sample, and it looks at 7 marker variants (SNPs, single nucleotide polymorphisms) in the genome that people inherit from their parents and have been associated with increased risk for breast cancer. These variations are very common in the population but have been shown to affect a woman’s risk of getting breast cancer. The test’s validity in identifying risk for breast cancer has been confirmed in a number of large, multinational studies including more than 10,000 patients and 30,000 controls.

According to the test results, only about 5% of women have an average 2-fold risk for breast cancer compared to the general population, and about 1% have a 3-fold risk. This translates for white women to a lifetime risk of 24% and 36%, respectively, versus the average population-based risk of 12%. It is estimated that these 7 markers together account for 60% of breast cancer (population attributable risk).

Breast cancers can be classified as either estrogen receptor positive (ER+) or estrogen receptor negative (ER-), depending on whether they contain certain proteins that allow the cancer to respond to the female sex hormone estrogen, which can make the breast tissues more susceptible to hormonal risk factors and drive small tumors into larger tumors. Several of the genetic variants examined by the deCODE BreastCancerTM test affect the chance that a breast tumor, if it arises, will be ER+ or ER-. At the same time, ER+ tumors may be more amenable to prevention by drugs that target the estrogen pathway, such as tamoxifen.

The deCODE BreastCancerTM test does not test for what is generally referred to as familial or inherited forms of breast cancer caused by rare mutations in breast cancer genes such as BRCA1, BRCA2, TP53, and PTEN. These mutations confer extremely high risks of breast cancer and occur only in rare families that may have exceptionally high numbers of breast cancer cases, often arising in younger women and sometimes along with ovarian cancer. Mutations in these genes need to be tested for separately under the guidance of a genetic counselor. However, for individuals who are known to carry mutations in these genes, the deCODE BreastCancerTM test provides additional information on their overall risk of breast cancer since some of the test markers are shown to influence the effect of these rare breast cancer gene mutations.

Genetics of breast cancer

Altogether about 20 to 30% of women who get breast cancer have a family member with the disease, meaning that 70 to 80% do not have a family history of breast cancer. Women who have a first-degree relative (mother or sister) with breast cancer are twice as likely as the general population to develop the disease themselves. This indicates that genetic predisposition plays a significant role in determining who gets breast cancer and who does not.

The genetics of breast cancer has 3 main presentations:

1) Hereditary or familial form of breast cancer segregating within families.
2) Families with as few as 2 cases and not with strong enough genetic effect to be obviously segregating as a hereditary condition.
3) Sporadic breast cancer, no family history of the disease.

In fact numbers 2 and 3 above may be difficult to distinguish since breast cancer is so common that most families will have 1 or more affected with the disease and it is often just a matter of the number of women and the degree of relatedness that are assessed that determine how many breast cancers will be ascertained in a family. Still there seems to be a measurable difference in the number and degree of relatives affected for estimation of risk in different modeling tools based measures of risk associated with positive family history and other recognized risk factors (see for example the Gail score model at http://www.cancer.gov/bcrisktool/).

Hereditary breast cancer
Only a portion of patients with a family history of breast cancer (less than 25%; 2 to 5% of all breast cancer cases) have what qualifies as the highly heritable or familial form of breast cancer caused by identifiable genetic mutations in the BRCA1, BRCA2, TP53, and PTEN genes. These individuals usually have a strong family history of breast cancer, particularly of early-onset and/or ovarian cancer cases. However, each of these mutations is very rare, occurring in only a very small fraction of breast cancer cases. The deCODE BreastCancerTM test does not include or detect these rare mutations. However some of the variants in the deCODE BreastCancerTM test modulate the risk of breast cancer in subjects who carry mutations in the BRCA1 and/or BRCA2 genes. The deCODE BreastCancerTM test reports a factor based on the relevant SNP genotypes by which the lifetime risk from the BRCA mutation should be multiplied in order to determine the overall lifetime genetic risk of breast cancer, given that the subject is diagnosed as a carrier of a high-penetrance BRCA1 or BRCA2 mutation.

Breast cancer cases with a not so noticeable family history
15 to 20 % of breast cancer cases have 1 or more close relatives with breast cancer but do not have so strong or characteristic family history as to be recognized as hereditary or familial, nor do they have mutations in the BRCA1, BRCA2, TP53, and PTEN genes. These patients may have heretofore unidentified genetic variants. The risk identified by the deCODE BreastCancerTM test seems to be largely independent of immediate family history, ie, the risk markers identified account for only a small portion (about 5%) of these familial cases. Thus the common genetic variants tested by the deCODE BreastCancerTM test do not explain risk due to family history of breast cancer. In fact, numerous studies have shown that the risk is independent of family history. This fact makes the deCODE BreastCancerTM test all the more relevant for this group of patients since their increased baseline risk caused by their family history and as assessed by some of the models available, can be multiplied by the test results.

Sporadic breast cancer
The majority (70 to 80%) of breast cancer cases arise in individuals who do not have a noticeable family history of breast cancer. This does not mean that these women are not genetically predisposed to develop breast cancer. The genetic predisposition variants they inherit may be so common in the population, of such a small number and each with such a relatively small effect, that their contribution to breast cancer generally surfaces as sporadic cases. On an individual basis however, women who have several of these genetic risk variants are at a substantially increased risk relative to the population. The deCODE BreastCancerTM test is designed to assess the genetic risk of the common form of breast cancer by testing for multiple risk variants that are common in the population and is especially useful in the 70 to 80% of the population that does not have a family history of breast cancer.

Collectively, the deCODE BreastCancerTM markers account for about 60% of the population attributable risk, meaning that if we were able to prevent all breast cancer cases in women that have increased risk relative to the general population according to the deCODE BreastCancerTM test, 60% of breast cancer would be eliminated.

In basic terms, carrying a high-risk deCODE BreastCancerTM genetic profile does not necessarily mean that the subject will develop breast cancer, just as having a low-risk genetic profile does not eliminate the possibility of getting the disease. Rather, these genetic risk variants impact the likelihood that the subject will develop breast cancer. Nongenetic risk factors such as current age, age at menarche, age at first live birth, hormonal history and status, history of exposure of the chest wall to X-rays, and previous benign or malignant breast disease may also affect a subject’s risk of breast cancer. Genetic and nongenetic risk factors all need to be taken into account when judging the overall breast cancer risk of an individual patient.

Risks Identified by deCODE BreastCancer™

The deCODE BreastCancer™ test assesses the genetic risk of breast cancer by testing for genetic risk variants that are very common in the population, each of which contribute relatively little, but that when combined can have a significant effect.

The deCODE BreastCancer™ test determines whether the subject has inherited the risk or non-risk version at 7 different variable sites in the human genome. By comparing deCODE BreastCancer™ to the general risk of women in the population it can be seen whether the person tested has a risk greater or lower than average population risk. The risks at each of the 7 markers are multiplied together to define combined risks of from 0.4- to about 4.0-fold the relative general population risk. The deCODE BreastCancerTM test examines only genetic risk factors, so other factors such as age and hormonal factors need to also be taken into account. By combining the test results and risks associated with other known risk factors a more complete lifetime risk estimate can be generated.

Based on an individual’s genotypes for the markers, lifetime genetic risk of being diagnosed with breast cancer can be determined and related to the general risk of breast cancer in the population. The deCODE BreastCancerTM test reports the subject’s measured genetic risk of breast cancer relative to the average population and the lifetime risk of being diagnosed with breast cancer.

The relative genetic risk of breast cancer compared to the general population determined by the test can vary from 0.45 for subjects who no risk variants at the 7 markers, to 3.77 for subjects who have 2 risk variants (1 on each chromosome) at all markers.

About 42% of the female population has genotype combinations of the tested markers that confer an increased relative risk (>1) of breast cancer. Ten percent of women in the general population have genotypes that confer a more than 40% increase in the relative risk of breast cancer, about 5% would be considered high risk with a 1.66-fold or greater risk (corresponding to a lifetime risk of 20% or greater), and approximately 1% of women have, on average, a 3-fold risk (37% lifetime risk of breast cancer).

The risk distribution in the general population and the proportion of the population with decreased (<1) and increased (>1) risks according to the test are given in the figure below:

In basic terms, carrying a high-risk deCODE BreastCancer™ genetic profile does not necessarily mean that a woman will develop breast cancer, just as having a low-risk genetic profile does not eliminate the possibility of getting the disease. Rather, these genetic risk variants impact the likelihood that she will develop breast cancer. Nongenetic risk factors such as current age, age at menarche, age at first live birth, hormonal history and status, history of exposure of the chest wall to X-rays, and previous benign or malignant breast disease may also affect a woman’s risk of breast cancer. Genetic and nongenetic risk factors all need to be taken into account when judging the overall breast cancer risk of an individual.

The deCODE ProstateCancer™ test is a novel, non-invasive, DNA-based reference laboratory test for the first genetic risk factors ever found to confer risk for a common type of cancer in the general population. These markers are not dependent on a family history of prostate cancer – in fact, they are independent of family history and the genetic risk of the ProstateCancer test multiples with the family risks mentioned above. All but one of the variants were discovered in Iceland and confirmed in several American and European ancestry cohorts but have also been confirmed in several other populations by independent research groups.

Genetic Markers

The deCODE ProstateCancer ™ test identifies eight known variants, three on chromosome 8 (in the 8q24 region), two on chromosome 17 (in regions 17q12 and 17q24.3), one on chromosome 2 (in the 2p15 region), one on chromosome 11 (the 11q13.3 region) and one on the X-chromosome (sex chromosome; Xp11.22) . Based on the presumption that these markers are independent, and the individual risks therefore multiply, the various genotype combinations have associated relative risks in the range of 0.33(non carriers for any of the risk markers) to 17.6 (homozygous for all of the eight risk variants) compared to the general population risk. Combined, these 8 variants appear to account for about half of the cases of prostate cancer (sometimes termed population attributable risk). About 40% of the population has a genotype combination of the tested markers that have an increased relative risk (>1) over the general population and about 10% of the population has a genotype combinations that confer an average two-fold relative risk and about 1% have relative risk above 3. One should be careful to apply extreme risk results to individuals since they are based on presumptions of a multiplicative model and are associated with genotype combinations that are extremely rare.

The risk distribution in the general population and the proportion of the population with higher and lower risk as the individual tested is given in the figure below.

Genetic risk assessment by deCODE ProstateCancer™ test
The results of the deCODE ProstateCancer are reported as the combined genetic risk associated with the individual’s genotype combination and as an individual lifetime risk compared to the population lifetime risk. A graph such as the one above will be provided that allows the individual’s risk results to be compared to risk and genotype distribution of the general population (see sample report on the “Result and report” web page). Note that deCODE ProstateCancer™ only measures these 8 validated genes. There are likely other genes that have not yet been discovered and there are other risk factors such as family history and ethnicity that need to be multiplied to this genetic risk to refine an individual’s risk.

Glaucoma is a heterogeneous group of disorders that share a distinct pattern of optic nerve damage. There are two basic forms of glaucoma, open- and closed angle glaucoma. In most populations, open-angle glaucoma, characterized by painless loss of vision, constitutes the majority of glaucoma cases. Open-angle glaucoma is defined as a progressive loss of neuroretinal rim tissue within the optic disk and consequent excavation of the optic disk with corresponding loss of visual field and is divided into primary open-angle glaucoma and secondary glaucoma. Primary open angle glaucoma is without an identifiable cause of aqueous outflow resistance, whereas in secondary glaucoma including exfoliation glaucoma, the outflow resistance is of a known cause. The prevalence of exfoliation glaucoma increases with age, and although the disease is found worldwide, a number of studies have pointed to a geographical clustering of the syndrome.

Exfoliation syndrome is the most common identifiable cause of secondary glaucoma in most populations. According to recent studies the 15-year risk of exfoliation syndrome conversion to exfoliation glaucoma is about 60%. Exfoliation glaucoma is characterized by rapid progression, high resistance to medical therapy, and a worse prognosis than in primary open angle glaucoma. Family history is an important risk factor for both primary open angle glaucoma and exfoliation syndrome which, together with ethnic differences in prevalence of primary open angle glaucoma, points to a role of genetic factors in the risk of suffering from these conditions.

The discovery of glaucoma genes provides a method for early detection of glaucoma. Genetic testing is capable of identifying those at highest risk for developing glaucoma. Such patients would include family members of patients with known glaucoma gene defects and members of families with a strong history of inherited glaucoma. About 10-30% of all primary open angle glaucoma patients have the LOXL1 glaucoma gene defect, but about 25 % of the general population (white Caucasians) are positive for the test Glaucoma gene testing of those who are at high risk for developing glaucoma may be of value followed by regular monitoring of the eye pressure by a physician.