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

• DOI: 10.1126/science.1142364
• Publication Date: 2007-04-27T01:03:40Z
• Authors: Eleftheria Zeggini; Michael N. Weedon; Cecilia M. Lindgren; Timothy M. Frayling; Katherine S. Elliott; Hana Lango; Nicholas J. Timpson; John R. B. Perry; Nigel W. Rayner; Rachel M. Freathy; Jeffrey C. Barrett; Beverley Shields; Andrew P. Morris; Sian Ellard; Christopher J. Gr...; Lorna W. Harries; Jonathan L. Marchini; Katharine R. Owen; Beatrice Knight; Lon R. Cardon; Mark Walker; Graham A. Hitman; Andrew D. Morris; Alex S. F. Doney; Mark I. McCarthy; Andrew T. Hattersley
• Keywords: TCF7L2; Genome-wide Association Study; Genetic Association

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 Wellcome Trust Case Control Consortium, we set out to detect replicated association signals through analysis 3757 additional 5346 integration our findings with equivalent other international consortia. We detected susceptibility loci around genes CDKAL1, CDKN2A/CDKN2B, IGF2BP2 confirmed recently described associations at HHEX/IDE SLC30A8. Our provide insight into genetic architecture diabetes, emphasizing contribution multiple variants modest effect. regions identified underscore importance pathways influencing pancreatic beta cell function etiology diabetes.