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, Chidambaram Manickam & 47 others Debashish Das, Elin Grundberg, Åsa 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

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 - Oct 2011
Externally publishedYes

Fingerprint

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

ASJC Scopus subject areas

  • Genetics

Cite this

Kooner, J. S., Saleheen, D., Sim, X., Sehmi, J., Zhang, W., Frossard, P., ... 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

Genome-wide association study in individuals of South Asian ancestry identifies six new type 2 diabetes susceptibility loci. / 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; Manickam, Chidambaram; Das, Debashish; Grundberg, Elin; Hedman, Åsa 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, 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.

In: Nature Genetics, Vol. 43, No. 10, 10.2011, p. 984-989.

Research output: Contribution to journalArticle

Kooner, JS, Saleheen, D, Sim, X, Sehmi, J, Zhang, W, Frossard, P, Been, LF, Chia, KS, Dimas, AS, Hassanali, N, Jafar, T, Jowett, JBM, Li, X, Radha, V, Rees, SD, Takeuchi, F, Young, R, Aung, T, Basit, A, Manickam, C, Das, D, Grundberg, E, Hedman, ÅK, 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, 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 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
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 ; Manickam, Chidambaram ; Das, Debashish ; Grundberg, Elin ; Hedman, Åsa 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, 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. / 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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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 - Manickam, Chidambaram

AU - Das, Debashish

AU - Grundberg, Elin

AU - Hedman, Åsa 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.

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AU - Rasheed, Asif

AU - Samuel, Maria

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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, M. Ann

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.

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