Journal
NATURE GENETICS
Volume 43, Issue 10, Pages 984-U94Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.921
Keywords
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Categories
Funding
- Wellcome Trust [070854/Z/03/Z, 080747/Z/06/Z, 083270/Z/07/Z, 084723/Z/08/Z]
- Chennai Wellingdon Corporate Foundation
- Diabetes UK [07/0003512]
- National Institute for Health Research Comprehensive Biomedical Research Centre at Imperial College Healthcare NHS Trust
- British Heart Foundation [SP/04/002]
- Medical Research Council [G0700931]
- National Institute for Health Research [RP-PG-0407-10371]
- US National Institutes of Health [DK-25446, KO1TW006087]
- KAKENHI
- Ministry of Education, Culture, Sports, Science and Technology of Japan
- National Center for Global Health and Medicine
- National Institute of Diabetes and Digestive and Kidney Diseases [R01DK082766]
- A*STAR Biomedical Research Council [05/1/21/19/425]
- Biomedical Research Council Singapore [09/1/35/19/616, 08/1/35/19/550]
- National Medical Research Council Singapore [NMRC/STaR/0003/2008, 1174/2008]
- National Science Foundation of Sri Lanka
- Oxford NIHR Biomedical Research Centre
- National Institutes of Health Research (NIHR) [RP-PG-0407-10371] Funding Source: National Institutes of Health Research (NIHR)
- British Heart Foundation [RG/08/014/24067] Funding Source: researchfish
- Medical Research Council [G0801056B, G0700931, G0801056, G0601966] Funding Source: researchfish
- National Institute for Health Research [RP-PG-0407-10371, NF-SI-0508-10272] Funding Source: researchfish
- MRC [G0700931, G0601966, G0801056] Funding Source: UKRI
- Wellcome Trust [080747/Z/06/Z] Funding Source: Wellcome Trust
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We carried out a genome-wide association study of type-2 diabetes (T2D) in individuals of South Asian ancestry. Our discovery set included 5,561 individuals with T2D (cases) and 14,458 controls drawn from studies in London, Pakistan and Singapore. We identified 20 independent SNPs associated with T2D at P < 10(-4) for testing in a replication sample of 13,170 cases and 25,398 controls, also all of South Asian ancestry. In the combined analysis, we identified common genetic variants at six loci (GRB14, ST6GAL1, VPS26A, HMG20A, AP3S2 and HNF4A) newly associated with T2D (P = 4.1 x 10(-8) to P = 1.9 x 10(-11)). SNPs at GRB14 were also associated with insulin sensitivity (P = 5.0 x 10(-4)), and SNPs at ST6GAL1 and HNF4A were also associated with pancreatic beta-cell function (P = 0.02 and P = 0.001, respectively). Our findings provide additional insight into mechanisms underlying T2D and show the potential for new discovery from genetic association studies in South Asians, a population with increased susceptibility to T2D.
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