Multiple type 2 diabetes susceptibility genes following genome-wide association scan in UK samples

• Published in: Science (American Association for the Advancement of Science) 2007-04, Vol.316 (5829), p.1336-1341
• Main Authors: 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., McCarthy, Mark I., Hattersley, Andrew T.
• Format: Article
• Language: English
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1142364

The molecular mechanisms involved in the development of type 2 diabetes are poorly understood. Starting from genome-wide genotype data for 1,924 diabetic cases and 2,938 population controls generated by the Wellcome Trust Case Control Consortium, we set out to detect replicated diabetes association signals through analysis of 3,757 additional cases and 5,346 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 insights 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.