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

被引：400

作者：

Kooner, Jaspal S. ^{[1
,2
,3
]}

Saleheen, Danish ^{[4
,5
]}

Sim, Xueling ^{[6
]}

Sehmi, Joban ^{[1
,2
]}

Zhang, Weihua

Frossard, Philippe ^{[4
]}

Been, Latonya F.

Chia, Kee-Seng ^{[6
,7
]}

Dimas, Antigone S. ^{[8
,9
]}

Hassanali, Neelam ^{[10
]}

Jafar, Tazeen ^{[11
,12
]}

Jowett, Jeremy B. M. ^{[13
]}

Li, Xinzhong ^{[2
]}

Radha, Venkatesan ^{[14
]}

Rees, Simon D. ^{[15
,16
]}

Takeuchi, Fumihiko ^{[17
]}

Young, Robin ^{[5
]}

Aung, Tin ^{[18
,19
]}

Basit, Abdul ^{[20
]}

Chidambaram, Manickam ^{[14
]}

Das, Debashish ^{[1
]}

Grundberg, Elin ^{[21
]}

Hedman, Asa K. ^{[9
]}

Hydrie, Zafar I. ^{[20
]}

Islam, Muhammed ^{[11
]}

Khor, Chiea-Chuen ^{[6
,19
,22
]}

Kowlessur, Sudhir ^{[23
]}

Kristensen, Malene M. ^{[13
]}

Liju, Samuel ^{[14
]}

Lim, Wei-Yen ^{[6
]}

Matthews, David R. ^{[10
]}

Liu, Jianjun ^{[22
]}

Morris, Andrew P. ^{[9
]}

Nica, Alexandra C. ^{[8
]}

Pinidiyapathirage, Janani M. ^{[24
]}

Prokopenko, Inga ^{[9
]}

Rasheed, Asif ^{[4
]}

Samuel, Maria ^{[4
]}

Shah, Nabi ^{[4
]}

Shera, A. Samad ^{[25
]}

Small, Kerrin S. ^{[21
,26
]}

Suo, Chen ^{[6
]}

Wickremasinghe, Ananda R. ^{[24
]}

Wong, Tien Yin ^{[18
,19
,27
]}

Yang, Mingyu ^{[28
]}

Zhang, Fan ^{[28
]}

Abecasis, Goncalo R. ^{[29
]}

Barnett, Anthony H. ^{[15
,16
]}

Caulfield, Mark ^{[30
]}

Deloukas, Panos ^{[26
]}

机构：

[1] Ealing Hosp Natl Hlth Serv NHS Trust, Middlesex, England

[2] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Natl Heart & Lung Inst, London, England

[3] Imperial Coll Healthcare NHS Trust, London, England

[4] Ctr Noncommunicable Dis Pakistan, Karachi, Pakistan

[5] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England

[6] Natl Univ Singapore, Ctr Mol Epidemiol, Singapore 117548, Singapore

[7] Natl Univ Singapore, Dept Epidemiol & Publ Hlth, Singapore 117548, Singapore

[8] Univ Geneva, Sch Med, Dept Genet Med & Dev, CH-1211 Geneva, Switzerland

[9] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England

[10] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Churchill Hosp, Oxford, England

[11] Aga Khan Univ, Dept Community Hlth Sci, Karachi, Pakistan

[12] Aga Khan Univ, Dept Med, Karachi, Pakistan

[13] Baker IDI Heart & Diabet Inst, Melbourne, Vic, Australia

[14] Madras Diabet Res Fdn, ICMR, Dept Mol Genet, Adv Ctr Genom Diabet, Madras, Tamil Nadu, India

[15] Univ Birmingham, Coll Med & Dent Sci, Birmingham, W Midlands, England

[16] Heart England NHS Fdn Trust, BioMed Res Ctr, Birmingham, W Midlands, England

[17] Natl Ctr Global Hlth & Med, Dept Gene Diagnost & Therapeut, Res Inst, Tokyo, Japan

[18] Natl Univ Singapore, Dept Ophthalmol, Singapore 117548, Singapore

[19] Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore

[20] Baqai Inst Diabetol & Endocrinol, Karachi, Pakistan

[21] Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England

[22] Agcy Sci Technol & Res, Genome Inst Singapore, Singapore, Singapore

[23] Minist Hlth, Port Louis, Mauritius

[24] Univ Kelaniya, Fac Med, Dept Publ Hlth, Ragama, Sri Lanka

[25] Diabet Assoc Pakistan, Karachi, Pakistan

[26] Wellcome Trust Sanger Inst, Hinxton, England

[27] Univ Melbourne, Ctr Eye Res Australia, Melbourne, Vic, Australia

[28] Beijing Genom Inst, Shenzhen, Peoples R China

[29] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA

[30] Queen Mary Univ London, Barts & London Sch Med, William Harvey Res Inst, Barts & London Genome Ctr, London, England

[31] Univ Exeter, Peninsula Med Sch, Inst Biomed & Clin Sci, Exeter, Devon, England

[32] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Sch Publ Hlth, London, England

[33] Univ Colombo, Diabet Res Unit, Dept Clin Med, Colombo, Sri Lanka

[34] Dr Mohans Diabet Specialties Ctr, Madras, Tamil Nadu, India

[35] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA

[36] Univ London Imperial Coll Sci Technol & Med, HPA, MRC, Ctr Environm & Hlth, London, England

[37] Natl Univ Singapore, Dept Stat & Appl Probabil, Singapore 117548, Singapore

[38] Natl Univ Singapore, Grad Sch Integrat Sci & Engn, Singapore 117548, Singapore

[39] Churchill Hosp, Oxford Natl Inst Hlth Res NIHR, Biomed Res Ctr, Oxford OX3 7LJ, England

[40] Natl Univ Singapore, Dept Med, Singapore 117548, Singapore

[41] Duke Natl Univ Singapore, Grad Sch Med, Singapore, Singapore

来源：

NATURE GENETICS | 2011年 / 43卷 / 10期

基金：

英国医学研究理事会; 英国惠康基金; 美国国家科学基金会; 美国国家卫生研究院;

关键词：

GENETIC-VARIATION; INSULIN-RESISTANCE; EXPRESSION; METHODOLOGY; PROTEINS; PATTERNS; STORAGE; OBESITY; GRB10; RISK;

D O I：

10.1038/ng.921

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：984 / U94

页数：8

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