Hints of Unique Genetic Effects for Type 2 Diabetes in India

Abstract

The prevalence of type 2 diabetes (T2D) is rising rapidly worldwide. In September 2012, the World Health Organization reported a global prevalence exceeding 300 million people, predicting a further 60–70% increase by the year 2030 (1). One of the largest absolute increases is expected to occur in India, with the International Diabetes Federation estimating that India alone will have 100 million people with diabetes by 2030 (2). About 90% of these will have T2D. Increased food consumption and decreased physical activity represent major contributors to the growing Indian T2D epidemic, reflecting ongoing economic transitions and widespread embrace of a Western lifestyle. But T2D risk also has a substantial genetic component and evidence indicates that Indians may be more susceptible to developing insulin resistance and T2D compared with European-ancestry individuals of equivalent age and BMI (3–5), suggesting the possibility of population-specific genetic or epigenetic risk factors. A recent, comprehensive genetic study provided compelling evidence for global genetic differentiation of T2D risk. In a survey of thousands of confirmed genetic associations, risk alleles for T2D demonstrated the most extreme population frequency differentiation among twelve common diseases studied (6). A clear gradient of T2D risk allele frequencies along continental paths of early human migration was evident, suggesting potential population-specific evolutionary adaptation to agricultural …