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

被引：1694

作者：

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.

机构：

[1] Univ Oxford, Churchill Hosp, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX3 7LJ, England

[2] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England

[3] PEninsula Med Sch, Inst Biomed & Clin Sci, Exeter EX1 2LU, Devon, England

[4] Peninsula Med Sch, Inst Biomed & Clin Sci, Diabet Genet Grp, Exeter EX2 5DW, Devon, England

[5] Univ Bristol, MRC, Ctr Casual Anal Translat Epidemiol, Bristol BS2 8PR, Avon, England

[6] Royal Devon & Exeter NHS FDn Trust, Genet Mol Lab, Exeter EX2 5DW, Devon, England

[7] Univ Oxford, Dept Stat, Oxford OX1 3TG, England

[8] Univ Newcastle, Sch Clin Med Sci, Diabet Res Grp, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England

[9] Barts & London Royal London Hosp, Ctr Diabet & Metab Med, London E1 1BB, England

[10] Univ Dundee, Ninewells Hosp & Med Sch, Div Med & Therapeut, Diabet Res Grp, Dundee DD1 9SY, Scotland

来源：

SCIENCE | 2007年 / 316卷 / 5829期

基金：

英国惠康基金; 英国医学研究理事会;

关键词：

D O I：

10.1126/science.1142364

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：1336 / 1341

页数：6

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