Genetic risk profiling for prediction of type 2 diabetes ΠPLOS Currents Evidence on Genomic Tests

Type 2 diabetes (T2D) is a common disease caused by a complex interplay between many genetic and environmental factors. Candidate gene studies and recent collaborative genome-wide association efforts revealed at least 38 common single nucleotide polymorphisms (SNPs) associated with increased risk of T2D. Genetic testing of multiple SNPs is considered a potentially useful tool for early detection of individuals at high diabetes risk leading to improved targeting of preventive interventions. Clinical Scenario Both a population-based approach and a targeted high-risk approach are recommended as strategies for prevention of T2D. Several recent guidelines advocate screening for individuals at risk to develop T2D followed by blood glucose measurements to detect individuals with impaired fasting glucose (IFG) or impaired glucose tolerance (IGT). [1] Genetic testing of a panel of SNPs may be useful in detecting such groups of high-risk individuals in whom screening for T2D could be optimized. Test Description Genetic susceptibility testing for T2D is currently offered by several commercial companies that use genome-wide scans to deliver information about risk for many common complex diseases (see Table 1 ). For example, deCODEme offers predictions for 50 complex diseases and non-disease phenotypes that vary from breast cancer, atrial fibrillation, T2D or psoriasis, to eye color and bitter taste perception. [2] Tests are available for purchase directly to the individual consumers, or through the request from a physician (see Table 2 ). Direct-to-consumer risk companies sell risk profiles that differ in the number of genetic markers included and in the exact SNPs used. For example, deCODEme uses 21 SNPs from the genome-wide scan to calculate the risk of T2D for individuals with European descent, 9 SNPs for East Asians and 2 SNPsfor African Americans. [3] A test based on the same markers is also available as a separate T2D profile. [4] Pathway Genomics offers also separate tests for individuals of African, Asian and Caucasian origin, [5] 23andMe uses 9 SNPs to determine the risk of developing T2D, [6] Navigenics tests18 SNPs, [7] and GeneticHealth, an UK based company, calculates the risk for obesity, diabetes and weight loss using the same 7 SNPs. [8] Genetic risks are calculated on the basis of literature data. The companies take an average risk from some epidemiological study and multiply this with the odds ratios from published meta-analyses or large scale genome-wide association studies. [9] Importantly, the companies do not use information about clinical risk factors when calculating the risk of disease. When available, some companies use sex, ethnicity and age matched population risks to depart from. Table 1. Direct-to-consumer companies that sell genetic tests for Type 2 Diabetes risk Table 2. Direct-to-consumer companies 1 PLOS Currents Evidence on Genomic Tests Legend Table 2 : CLIA, Clinical Laboratory Improvement Amendments of 1988; DTC, direct-to-consumer. Public Health Importance T2D is a metabolic disorder characterized by hyperglycemia, insulin resistance and relative insulin deficiency. Diabetes is a leading cause of blindness, renal failure and limb amputation, and a major risk factor for cardiovascular morbidity and mortality. [10] It is estimated that approximately 285 million people worldwide will have diabetes in 2010. This number is expected to increase by more than 50% in the next 20 years if no preventive strategies are implemented. [11] Diabetes is responsible for almost four million deaths worldwide in the 20-79 age group in 2010, representing 6.8% of global all-cause mortality in this age group. [11] Preventive interventions for T2D, including medication, weight loss and increased physical activity, can slow or even reverse the disease process. [12] For example, the United States Diabetes Prevention Program trial investigated the efficacy of intensive lifestyle interventions or metformin treatment compared to standard lifestyle recommendations. [13] Lifestyle intervention resulted in 58% T2D risk reduction compared to the placebo arm, at 2.8 years of follow-up. For the same follow-up, metformin resulted in 31% T2D risk reduction. [13] Genetic tests are claimed by the DTC companies to improve risk prediction and increase adherence to preventive interventions (e.g., “Knowledge is self-empowering and it can motivate you towards taking steps that reduce other risk factors, which have been found to contribute to your genetic predisposition risk” [14] ), thus helping to improve outcomes and reduce the costs and burden of disease for society (e.g., “The conditions included in Navigenics’ analysis are those that are clinically actionable and those that contribute to the major burden of disease in the United States, such as myocardial infarction, cancer, and type 2 diabetes.” [15] ) Published Reviews, Recommendations and Guidelines Systematic evidence reviews None identified. Recommendations by independent group None identified. Guidelines by professional groups