Replication of Genome-Wide Association Signals in UK Samples Reveals Risk Loci for Type 2 Diabetes-Reference-Cited by-同舟云学术

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

Published:2007-06 Issue:5829 Volume:316 Page:1336-1341
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Zeggini Eleftheria¹²³⁴⁵,Weedon Michael N.¹²³⁴⁵,Lindgren Cecilia M.¹²³⁴⁵,Frayling Timothy M.¹²³⁴⁵,Elliott Katherine S.¹²³⁴⁵,Lango Hana¹²³⁴⁵,Timpson Nicholas J.¹²³⁴⁵,Perry John R. B.¹²³⁴⁵,Rayner Nigel W.¹²³⁴⁵,Freathy Rachel M.¹²³⁴⁵,Barrett Jeffrey C.¹²³⁴⁵,Shields Beverley¹²³⁴⁵,Morris Andrew P.¹²³⁴⁵,Ellard Sian¹²³⁴⁵,Groves Christopher J.¹²³⁴⁵,Harries Lorna W.¹²³⁴⁵,Marchini Jonathan L.¹²³⁴⁵,Owen Katharine R.¹²³⁴⁵,Knight Beatrice¹²³⁴⁵,Cardon Lon R.¹²³⁴⁵,Walker Mark¹²³⁴⁵,Hitman Graham A.¹²³⁴⁵,Morris Andrew D.¹²³⁴⁵,Doney Alex S. F.¹²³⁴⁵,McCarthy Mark I.¹²³⁴⁵,Hattersley Andrew T.¹²³⁴⁵

Affiliation:

1. Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, OX3 7LJ, UK.

2. The Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, OX37BN, UK.

3. Genetics of Complex Traits, Institute of Biomedical and Clinical Science, Peninsula Medical School, Magdalen Road, Exeter EX1 2LU, UK.

4. Diabetes Genetics Group, Institute of Biomedical and Clinical Science, Peninsula Medical School, Barrack Road, Exeter EX2 5DW, UK.

5. Medical Research Council Centre for Causal Analyses in Translational Epidemiology, Bristol University, Canynge Hall, Whiteladies Rd, Bristol, BS2 8PR, UK.

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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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