Replication of Genome-Wide Association Signals in UK Samples Reveals Risk Loci for Type 2 Diabetes

TLDR

The molecular mechanisms underlying type 2 diabetes remain poorly understood. The study aimed to detect replicated diabetes association signals by analyzing additional cases and controls and integrating data from international consortia. The authors used genome‑wide genotype data from 1,924 cases and 2,938 controls from the Wellcome Trust Case Control Consortium, followed by analysis of 3,757 additional cases and 5,346 controls. The study identified susceptibility loci near CDKAL1, CDKN2A/CDKN2B, IGF2BP2, HHEX/IDE, and SLC30A8, highlighting multiple modest‑effect variants and pathways affecting pancreatic β‑cell development and function.

Abstract

The molecular mechanisms involved in the development of type 2 diabetes are poorly understood. Starting from genome-wide genotype data for 1924 diabetic cases and 2938 population controls generated by the Wellcome Trust Case Control Consortium, we set out to detect replicated diabetes association signals through analysis of 3757 additional cases and 5346 controls and by integration of our findings with equivalent data from other international consortia. We detected diabetes susceptibility loci in and around the genes CDKAL1, CDKN2A/CDKN2B, and IGF2BP2 and confirmed the recently described associations at HHEX/IDE and SLC30A8. Our findings provide insight into the genetic architecture of type 2 diabetes, emphasizing the contribution of multiple variants of modest effect. The regions identified underscore the importance of pathways influencing pancreatic beta cell development and function in the etiology of type 2 diabetes.