Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes by Zeggini Eleftheria, Weedon Michael N, Lindgren Cecilia M, Frayling Timothy M, Elliott Katherine S, Lango Hana, Timpson Nicholas J, Perry John R B, Rayner Nigel W, Freathy Rachel M, Barrett Jeffrey C, Shields Beverley, Morris Andrew P, Ellard Sian, Groves Christopher J, Harries Lorna W, Marchini Jonathan L, Owen Katharine R, Knight Beatrice, Cardon Lon R, Walker Mark, Hitman Graham A, Morris Andrew D, Doney Alex S F, Wellcome Trust Case Control Consortium (WTCCC), McCarthy Mark I, Hattersley Andrew T in Science (New York, N.Y.) (2007). PubMed

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.

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