Genome-Wide Association Analysis Identifies Loci for Type 2 Diabetes and Triglyceride Levels

TLDR

Improved insight into the etiology of type 2 diabetes is needed to develop better prevention and treatment strategies. The study genotyped 386,731 common SNPs in 1,464 T2D patients and 1,467 matched controls, assessing glucose metabolism, lipids, obesity, and blood pressure. The analysis confirmed three novel T2D loci (near CDKN2A/B, IGF2BP2, CDKAL1) and replicated associations near HHEX and SLC30A8, identified a GCKR intronic SNP linked to triglycerides, and demonstrated that GWAS can uncover pathogenic clues in noncoding regions.

Abstract

New strategies for prevention and treatment of type 2 diabetes (T2D) require improved insight into disease etiology. We analyzed 386,731 common single-nucleotide polymorphisms (SNPs) in 1464 patients with T2D and 1467 matched controls, each characterized for measures of glucose metabolism, lipids, obesity, and blood pressure. With collaborators (FUSION and WTCCC/UKT2D), we identified and confirmed three loci associated with T2D-in a noncoding region near CDKN2A and CDKN2B, in an intron of IGF2BP2, and an intron of CDKAL1-and replicated associations near HHEX and in SLC30A8 found by a recent whole-genome association study. We identified and confirmed association of a SNP in an intron of glucokinase regulatory protein (GCKR) with serum triglycerides. The discovery of associated variants in unsuspected genes and outside coding regions illustrates the ability of genome-wide association studies to provide potentially important clues to the pathogenesis of common diseases.