Prediction of type 2 diabetes: the dawn of polygenetic testing for complex disease

Excerpt

Advances in the search for the genetic determinants of type 2 diabetes have led, in recent years, to the discovery of dozens of risk loci, with many more expected to be found [1‐3]. Each individual locus has a relatively small effect, increasing the risk of diabetes by ~5–40% per risk allele. Although the risk alleles themselves are common, few individuals (~10%) are homozygous at a given locus, no locus accounts for more than a fraction of a per cent of the variance in the risk of diabetes, and only a few loci have a proven function in diabetes pathogenesis [4]. It seems apparent that revelation of novel pathways determining energy metabolism will come from this era of diabetes gene discovery. However, how to apply this new knowledge to improve clinical and public health is less clear. Approaches to genetic testing and counselling for diseases with multiple common loci that exert a modest effect are not well established. The influence of genetic risk knowledge on personal health behaviours for chronic disease prevention or treatment is not known. Meanwhile, there is growing enthusiasm for the use of new genetic knowledge in disease screening and diagnostic testing [5]. In contrast to uncertainties about prevention and personalisation, the value of current genetic knowledge for prediction of diabetes risk is becoming fairly clear. …