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 B. M. Jowett; Xinzhong Li; Venkatesan Radha; Simon D. Rees; Fumihiko Takeuchi; Robin Young; Tin Aung; Abdul Basit; Manickam Chidambaram; Debashish Das; Elin Grundberg; Asa K. Hedman; Zafar I. Hydrie; Muhammed Islam; Chiea-Chuen Khor; Sudhir Kowlessur; Malene M. Kristensen; Samuel Liju; Wei-Yen Lim; David R. Matthews; Jianjun Liu; Andrew P. Morris; Alexandra C. Nica; Janani M. Pinidiyapathirage; Inga Prokopenko; Asif Rasheed; Maria Samuel; Nabi Shah; A. Samad Shera; Kerrin S. Small; Chen Suo; Ananda R. Wickremasinghe; Tien Yin Wong; Mingyu Yang; Fan Zhang; Goncalo R. Abecasis; Anthony H. Barnett; Mark Caulfield; Panos Deloukas; Timothy M. Frayling; Philippe Froguel; Norihiro Kato; Prasad Katulanda; M. Ann Kelly; Junbin Liang; Viswanathan Mohan; Dharambir K. Sanghera; James Scott; Mark Seielstad; Paul Z. Zimmet; Paul Elliott; Yik Ying Teo; Mark I. McCarthy; John Danesh; E. Shyong Tai; John C. Chambers; DIAGRAM

doi:10.1038/ng.921

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

Journal article

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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, …

Nature genetics, Vol.43(10), pp.984-U94

01/10/2011

DOI: https://doi.org/10.1038/ng.921

PMID: 21874001

Abstract

Genetics & Heredity

Life Sciences & Biomedicine

Science & Technology

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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Title: Genome-wide association study in individuals of South Asian ancestry identifies six new type 2 diabetes susceptibility loci
Creators: Jaspal S. Kooner - Imperial College London
Danish Saleheen - Center for Non-Communicable Diseases
Xueling Sim - National University of Singapore
Joban Sehmi - Ealing Hospital
Weihua Zhang - Imperial College London
Philippe Frossard - Center for Non-Communicable Diseases
Latonya F. Been - University of Oklahoma Health Sciences Center
Kee-Seng Chia - Natl Univ Singapore, Ctr Mol Epidemiol, Singapore 117548, Singapore
Antigone S. Dimas - University of Geneva
Neelam Hassanali - Churchill Hospital
Tazeen Jafar - Aga Khan University
Jeremy B. M. Jowett - Baker Heart and Diabetes Institute
Xinzhong Li - University of London
Venkatesan Radha - Madras Diabetes Research Foundation
Simon D. Rees - University of Birmingham
Fumihiko Takeuchi - National Center for Global Health and Medicine
Robin Young - University of Cambridge
Tin Aung - Duke-NUS Medical School
Abdul Basit - Baqai Institute of Diabetology and Endocrinology
Manickam Chidambaram - Madras Diabetes Research Foundation
Debashish Das - Ealing Hospital
Elin Grundberg - King's College London
Asa K. Hedman - University of Oxford
Zafar I. Hydrie - Baqai Inst Diabetol & Endocrinol, Karachi, Pakistan
Muhammed Islam - Aga Khan University
Chiea-Chuen Khor - National University of Singapore
Sudhir Kowlessur - Ministry of Health and Quality of Life
Malene M. Kristensen - Baker Heart and Diabetes Institute
Samuel Liju - Madras Diabetes Research Foundation
Wei-Yen Lim - Natl Univ Singapore, Ctr Mol Epidemiol, Singapore 117548, Singapore
David R. Matthews - Churchill Hospital
Jianjun Liu - Genome Institute of Singapore
Andrew P. Morris - University of Oxford
Alexandra C. Nica - University of Geneva
Janani M. Pinidiyapathirage - University of Kelaniya
Inga Prokopenko - University of Oxford
Asif Rasheed - Center for Non-Communicable Diseases
Maria Samuel - Center for Non-Communicable Diseases
Nabi Shah - Center for Non-Communicable Diseases
A. Samad Shera - Diabet Assoc Pakistan, Karachi, Pakistan
Kerrin S. Small - King's College London
Chen Suo - National University of Singapore
Ananda R. Wickremasinghe - University of Kelaniya
Tien Yin Wong - National University of Singapore
Mingyu Yang - Beijing Genom Inst, Shenzhen, Peoples R China
Fan Zhang - BGI Group
Goncalo R. Abecasis - University of Michigan–Ann Arbor
Anthony H. Barnett - University of Birmingham
Mark Caulfield - William Harvey Research Institute
Panos Deloukas - Wellcome Sanger Institute
Timothy M. Frayling - University of Exeter
Philippe Froguel - Imperial College London
Norihiro Kato - National Center for Global Health and Medicine
Prasad Katulanda - Oxford Centre for Diabetes, Endocrinology and Metabolism
M. Ann Kelly - University of Birmingham
Junbin Liang - BGI Group
Viswanathan Mohan - Madras Diabetes Research Foundation
Dharambir K. Sanghera - University of Oklahoma Health Sciences Center
James Scott - University of London
Mark Seielstad - University of California, San Francisco
Paul Z. Zimmet - Baker Heart and Diabetes Institute
Paul Elliott - Medical Research Council
Yik Ying Teo - Agency for Science, Technology and Research
Mark I. McCarthy - Churchill Hospital
John Danesh - University of Cambridge
E. Shyong Tai - National University of Singapore
John C. Chambers - Imperial College London
DIAGRAM
Publication Details: Nature genetics, Vol.43(10), pp.984-U94
Publisher: Springer Nature
Number of pages: 8
Date published: 01/10/2011
Grant note: SP/04/002 / British Heart Foundation DK-25446; KO1TW006087 / US National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA NMRC/STaR/0003/2008; 1174/2008 / National Medical Research Council Singapore; National Medical Research Council, Singapore; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) G0700931; G0801056; G0601966 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) RP-PG-0407-10371; NF-SI-0508-10272 / National Institute for Health Research; National Institutes of Health Research (NIHR) 07/0003512 / Diabetes UK Ministry of Education, Culture, Sports, Science and Technology of Japan; Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT) National Science Foundation of Sri Lanka G0700931 / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) Oxford NIHR Biomedical Research Centre; National Institutes of Health Research (NIHR)
Identifiers: 99928695002346
Academic Unit: School of Biosciences
Language: English
Resource Type: Journal article

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

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