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

DIAGRAM, Jaspal S. Kooner (Lead / Corresponding author), 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 & 48 others 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, Ann M. 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

Research output: Contribution to journalArticle

316 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)984-989
Number of pages6
JournalNature Genetics
Volume43
Issue number10
DOIs
Publication statusPublished - 28 Aug 2011

Fingerprint

Genome-Wide Association Study
Type 2 Diabetes Mellitus
Single Nucleotide Polymorphism
Pakistan
Singapore
Insulin-Secreting Cells
Genetic Association Studies
Insulin Resistance
Population

Keywords

  • Asian Continental Ancestry Group/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

Cite this

DIAGRAM, Kooner, J. S., Saleheen, D., Sim, X., Sehmi, J., Zhang, W., ... Chambers, J. C. (2011). Genome-wide association study in individuals of South Asian ancestry identifies six new type 2 diabetes susceptibility loci. Nature Genetics, 43(10), 984-989. https://doi.org/10.1038/ng.921
DIAGRAM ; Kooner, Jaspal S. ; 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 ; Abecasis, Goncalo R. ; Barnett, Anthony H ; Caulfield, Mark ; Deloukas, Panos ; Frayling, Timothy M. ; Froguel, Philippe ; Kato, Norihiro ; Katulanda, Prasad ; Kelly, Ann M. ; 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. / Genome-wide association study in individuals of South Asian ancestry identifies six new type 2 diabetes susceptibility loci. In: Nature Genetics. 2011 ; Vol. 43, No. 10. pp. 984-989.
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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.",
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DIAGRAM, Kooner, JS, Saleheen, D, Sim, X, Sehmi, J, Zhang, W, Frossard, P, Been, LF, Chia, K-S, Dimas, AS, Hassanali, N, Jafar, T, Jowett, JBM, 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, C-C, Kowlessur, S, Kristensen, MM, Liju, S, Lim, W-Y, 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, Abecasis, GR, Barnett, AH, Caulfield, M, Deloukas, P, Frayling, TM, Froguel, P, Kato, N, Katulanda, P, Kelly, AM, Liang, J, Mohan, V, Sanghera, DK, Scott, J, Seielstad, M, Zimmet, PZ, Elliott, P, Teo, Y-Y, McCarthy, MI, Danesh, J, Tai, ES & Chambers, JC 2011, 'Genome-wide association study in individuals of South Asian ancestry identifies six new type 2 diabetes susceptibility loci', Nature Genetics, vol. 43, no. 10, pp. 984-989. https://doi.org/10.1038/ng.921

Genome-wide association study in individuals of South Asian ancestry identifies six new type 2 diabetes susceptibility loci. / DIAGRAM; Kooner, Jaspal S. (Lead / Corresponding author); 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; Abecasis, Goncalo R.; Barnett, Anthony H; Caulfield, Mark; Deloukas, Panos; Frayling, Timothy M.; Froguel, Philippe; Kato, Norihiro; Katulanda, Prasad; Kelly, Ann M.; 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. (Lead / Corresponding author).

In: Nature Genetics, Vol. 43, No. 10, 28.08.2011, p. 984-989.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Genome-wide association study in individuals of South Asian ancestry identifies six new type 2 diabetes susceptibility loci

AU - DIAGRAM

AU - Kooner, Jaspal S.

AU - Saleheen, Danish

AU - Sim, Xueling

AU - Sehmi, Joban

AU - Zhang, Weihua

AU - Frossard, Philippe

AU - Been, Latonya F.

AU - Chia, Kee-Seng

AU - Dimas, Antigone S.

AU - Hassanali, Neelam

AU - Jafar, Tazeen

AU - Jowett, Jeremy B. M.

AU - Li, Xinzhong

AU - Radha, Venkatesan

AU - Rees, Simon D.

AU - Takeuchi, Fumihiko

AU - Young, Robin

AU - Aung, Tin

AU - Basit, Abdul

AU - Chidambaram, Manickam

AU - Das, Debashish

AU - Grundberg, Elin

AU - Hedman, Asa K.

AU - Hydrie, Zafar I.

AU - Islam, Muhammed

AU - Khor, Chiea-Chuen

AU - Kowlessur, Sudhir

AU - Kristensen, Malene M.

AU - Liju, Samuel

AU - Lim, Wei-Yen

AU - Matthews, David R.

AU - Liu, Jianjun

AU - Morris, Andrew P.

AU - Nica, Alexandra C.

AU - Pinidiyapathirage, Janani M.

AU - Prokopenko, Inga

AU - Rasheed, Asif

AU - Samuel, Maria

AU - Shah, Nabi

AU - Shera, A. Samad

AU - Small, Kerrin S.

AU - Suo, Chen

AU - Wickremasinghe, Ananda R.

AU - Wong, Tien Yin

AU - Yang, Mingyu

AU - Zhang, Fan

AU - Abecasis, Goncalo R.

AU - Barnett, Anthony H

AU - Caulfield, Mark

AU - Deloukas, Panos

AU - Frayling, Timothy M.

AU - Froguel, Philippe

AU - Kato, Norihiro

AU - Katulanda, Prasad

AU - Kelly, Ann M.

AU - Liang, Junbin

AU - Mohan, Viswanathan

AU - Sanghera, Dharambir K.

AU - Scott, James

AU - Seielstad, Mark

AU - Zimmet, Paul Z.

AU - Elliott, Paul

AU - Teo, Yik-Ying

AU - McCarthy, Mark I.

AU - Danesh, John

AU - Tai, E. Shyong

AU - Chambers, John C.

PY - 2011/8/28

Y1 - 2011/8/28

N2 - 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.

AB - 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.

KW - Asian Continental Ancestry Group/genetics

KW - Case-Control Studies

KW - Diabetes Mellitus, Type 2/genetics

KW - Female

KW - Gene Expression Regulation

KW - Genetic Predisposition to Disease

KW - Genetics, Population

KW - Genome, Human

KW - Genome-Wide Association Study

KW - Humans

KW - Linkage Disequilibrium

KW - London

KW - Male

KW - Pakistan

KW - Polymorphism, Single Nucleotide

KW - Quantitative Trait Loci

KW - Singapore

U2 - 10.1038/ng.921

DO - 10.1038/ng.921

M3 - Article

VL - 43

SP - 984

EP - 989

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 10

ER -