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Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes

Lookup NU author(s): Professor Mark Walker, Professor John IsaacsORCiD

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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.


Publication metadata

Author(s): Zeggini E, Weedon MN, Lindgren CM, Frayling TM, Elliott KS, Lango H, Timpson NJ, Perry JRB, Rayner NW, Freathy RM, Barrett JC, Shields B, Morris AP, Ellard S, Groves CJ, Harries LW, Marchini JL, Owen KR, Knight B, Cardon LR, Walker M, Hitman GA, Morris AD, Doney ASF, The Wellcome Trust Case Control Consortium (WTCCC), McCarthy MI, Hattersley AT

Publication type: Article

Publication status: Published

Journal: Science

Year: 2007

Volume: 316

Issue: 5829

Pages: 1336-1341

ISSN (print): 0036-8075

ISSN (electronic): 1095-9203

Publisher: American Association for the Advancement of Science

URL: http://dx.doi.org/10.1126/science.1142364

DOI: 10.1126/science.1142364

PubMed id: 17463249


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Funding

Funder referenceFunder name
Wellcome Trust
083948Wellcome Trust
090532Wellcome Trust
G0000934Medical Research Council
G0500070Medical Research Council

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