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| Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes |
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| Author(s): Zeggini E (Zeggini, Eleftheria), Weedon MN (Weedon, Michael N.), Lindgren CM (Lindgren, Cecilia M.), Frayling TM (Frayling, Timothy M.), Elliott KS (Elliott, Katherine S.), Lango H (Lango, Hana), Timpson NJ (Timpson, Nicholas J.), Perry JRB (Perry, John R. B.), Rayner NW (Rayner, Nigel W.), Freathy RM (Freathy, Rachel M.), Barrett JC (Barrett, Jeffrey C.), Shields B (Shields, Beverley), Morris AP (Morris, Andrew P.), Ellard S (Ellard, Sian), Groves CJ (Groves, Christopher J.), Harries LW (Harries, Lorna W.), Marchini JL (Marchini, Jonathan L.), Owen KR (Owen, Katharine R.), Knight B (Knight, Beatrice), Cardon LR (Cardon, Lon R.), Walker M (Walker, Mark), Hitman GA (Hitman, Graham A.), Morris AD (Morris, Andrew D.), Doney ASF (Doney, Alex S. F.), McCarthy MI (McCarthy, Mark I.), Hattersley AT (Hattersley, Andrew T.) |
| Source: SCIENCE Volume: 316 Issue: 5829 Pages: 1336-1341 Published: JUN 1 2007 |
| Times Cited: 589 References: 25 |
| 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. |
| Document Type: Article |
| Language: English |
| Reprint Address: McCarthy, MI (reprint author), Univ Oxford, Churchill Hosp, Oxford Ctr Diabet Endocrinol & Metab, S Parks Rd, Oxford OX3 7LJ, England |
Addresses:
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 |
| Publisher: AMER ASSOC ADVANCEMENT SCIENCE, 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: 173PS |
| ISSN: 0036-8075 |
| DOI: 10.1126/science.1142364 |
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