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PMID: 21874001 Published · epublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Nature genetics ·Vol. 43 ·No. 10 ·2011-08-28 ·Pages 984-9

Kooner JS, Saleheen D, Sim X, Sehmi J, Zhang W, Frossard P, Been LF, Chia KS, Dimas AS, Hassanali N, Jafar T, Jowett JB, Li X, Radha V, Rees SD, Takeuchi F, Young R, Aung T, Basit A, Chidambaram M, Das D, Grundberg E, Hedman AK, Hydrie ZI, Islam M, Khor CC, Kowlessur S, Kristensen MM, Liju S, Lim WY, Matthews DR, Liu J, Morris AP, Nica AC, Pinidiyapathirage JM, Prokopenko I, Rasheed A, Samuel M, Shah N, Shera AS, Small KS, Suo C, Wickremasinghe AR, Wong TY, Yang M, Zhang F, DIAGRAM, MuTHER, Abecasis GR, Barnett AH, Caulfield M, Deloukas P, Frayling TM, Froguel P, Kato N, Katulanda P, Kelly MA, Liang J, Mohan V, Sanghera DK, Scott J, Seielstad M, Zimmet PZ, Elliott P, Teo YY, McCarthy MI, Danesh J, Tai ES, Chambers JC

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 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.

MeSH Terms
Asians/genetics Case-Control Studies Diabetes Mellitus, Type 2/genetics Female Gene Expression Regulation Genetic Predisposition to Disease Genetics, Population Genome, Human Genome-Wide Association Study Humans Linkage Disequilibrium London Male Pakistan Polymorphism, Single Nucleotide Quantitative Trait Loci Singapore
Authors & Affiliations
69 authors, click to expand affiliations / ORCID
Kooner Jaspal S
National Heart and Lung Institute (NHLI), Imperial College London, Hammersmith Hospital, London, UK. [email protected]
Saleheen Danish
Sim Xueling
Sehmi Joban
Zhang Weihua
Frossard Philippe
Been Latonya F
Chia Kee-Seng
Dimas Antigone S
Hassanali Neelam
Jafar Tazeen
Jowett Jeremy B M
Li Xinzhong
Radha Venkatesan
Rees Simon D
Takeuchi Fumihiko
Young Robin
Aung Tin
Basit Abdul
Chidambaram Manickam
Das Debashish
Grundberg Elin
Hedman Asa K
Hydrie Zafar I
Islam Muhammed
Khor Chiea-Chuen
Kowlessur Sudhir
Kristensen Malene M
Liju Samuel
Lim Wei-Yen
Matthews David R
Liu Jianjun
Morris Andrew P
Nica Alexandra C
Pinidiyapathirage Janani M
Prokopenko Inga
Rasheed Asif
Samuel Maria
Shah Nabi
Shera A Samad
Small Kerrin S
Suo Chen
Wickremasinghe Ananda R
Wong Tien Yin
Yang Mingyu
Zhang Fan
DIAGRAM
MuTHER
Abecasis Goncalo R
Barnett Anthony H
Caulfield Mark
Deloukas Panos
Frayling Timothy M
Froguel Philippe
Kato Norihiro
Katulanda Prasad
Kelly M Ann
Liang Junbin
Mohan Viswanathan
Sanghera Dharambir K
Scott James
Seielstad Mark
Zimmet Paul Z
Elliott Paul
Teo Yik Ying
McCarthy Mark I
Danesh John
Tai E Shyong
Chambers John C
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Article Info
Journal
Nature genetics
Abbr.
Nat Genet
ISSN
1546-1718
DOI
10.1038/ng.921
Email
[email protected]
Published
2011-08-28
Epub
2011-00-28
Pages
984-9
Language
English
Region
United States
NLM ID
9216904
PMCID
PMC3773920
Subset
IM
Grants
Medical Research Council · G0801056 · United Kingdom
British Heart Foundation · SP/04/002 · United Kingdom
NIDDK NIH HHS · R01 DK082766 · United States
Wellcome Trust · 083270/Z/07/Z · United Kingdom
Wellcome Trust · 079643 · United Kingdom
Wellcome Trust · 090532 · United Kingdom
Wellcome Trust · 070854/Z/03/Z · United Kingdom
NIDDK NIH HHS · DK-25446 · United States
NIDDK NIH HHS · R01DK082766 · United States
Wellcome Trust · 084723/Z/08/Z · United Kingdom
Medical Research Council · G0700931 · United Kingdom
Medical Research Council · G0601966 · United Kingdom
FIC NIH HHS · KO1TW006087 · United States
British Heart Foundation · RG/08/014/24067 · United Kingdom
Wellcome Trust · 080747/Z/06/Z · United Kingdom
Department of Health · RP-PG-0407-10371 · United Kingdom
FIC NIH HHS · K01 TW006087 · United States
External Links
PubMed source DOI: 10.1038/ng.921 PMC Full Text View journal details
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