Insights into the genetic susceptibility to type 2 diabetes from genome-wide association studies of glycaemic traits

Abstract

Over the past 8 years, the genetics of complex traits have benefited from an unprecedented advancement in the identification of common variant loci for diseases such as type 2 diabetes (T2D). The ability to undertake genome-wide association studies in large population-based samples for quantitative glycaemic traits has permitted us to explore the hypothesis that models arising from studies in non-diabetic individuals may reflect mechanisms involved in the pathogenesis of diabetes. Amongst 88 T2D risk and 72 glycaemic trait loci, only 29 are shared and show disproportionate magnitudes of phenotypic effects. Important mechanistic insights have been gained regarding the physiological role of T2D loci in disease predisposition through the elucidation of their contribution to glycaemic trait variability. Further investigation is warranted to define causal variants within these loci, including functional characterisation of associated variants, to dissect their role in disease mechanisms and to enable clinical translation.