Journal article

Genome-wide association study in individuals of South Asian ancestry identifies six new type 2 diabetes susceptibility loci

Jaspal S Kooner, Danish Saleheen, Xueling Sim, Joban Sehmi, Weihua Zhang, Philippe Frossard, Latonya F Been, Kee-Seng Chia, Antigone S Dimas, Neelam Hassanali, Tazeen Jafar, Jeremy BM Jowett, Xinzhong Li, Venkatesan Radha, Simon D Rees, Fumihiko Takeuchi, Robin Young, Tin Aung, Abdul Basit, Manickam Chidambaram Show all

Nature Genetics | NATURE PUBLISHING GROUP | Published : 2011

Abstract

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 × 10(-8) to P = 1.9 × 10(-11)). SNPs at GRB14 were also associated with insulin sensitivity (P = 5.0 × 10(-4)), and ..

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Grants

Awarded by Wellcome Trust


Awarded by Diabetes UK


Awarded by British Heart Foundation


Awarded by Medical Research Council


Awarded by National Institute for Health Research


Awarded by US National Institutes of Health


Awarded by National Institute of Diabetes and Digestive and Kidney Diseases


Awarded by A*STAR Biomedical Research Council


Awarded by Biomedical Research Council Singapore


Awarded by National Medical Research Council Singapore


Awarded by FOGARTY INTERNATIONAL CENTER


Awarded by NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES


Funding Acknowledgements

We would like to thank the many colleagues who contributed to collection and phenotypic characterization of the clinical samples as well as genotyping and analysis of the GWAS data. We would also like to acknowledge those individuals who agreed to participate in these studies. Major funding for the work described in this paper comes from Wellcome Trust awards (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); KAKENHI (Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan; National Center for Global Health and Medicine; US National Institutes of Health (KO1TW006087); 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; and Oxford NIHR Biomedical Research Centre. A full list of acknowledgments is provided in the Supplementary Note.