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; DIAGRAM Consortium; Marilyn Kelly

doi:10.1038/ng.921

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 ChidambaramDebashish 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, DIAGRAM Consortium, Marilyn Kelly

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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.

Original language	English
Pages (from-to)	984-989
Number of pages	6
Journal	Nature Genetics
Volume	43
Issue number	10
DOIs	https://doi.org/10.1038/ng.921
Publication status	Published - 28 Aug 2011

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10.1038/ng.921

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Kooner, J. S., Saleheen, D., Sim, X., Sehmi, J., Zhang, W., Frossard, P., Been, L. F., Chia, K.-S., Dimas, A. S., Hassanali, N., Jafar, T., Jowett, J. B. M., Li, X., Radha, V., Rees, S. D., Takeuchi, F., Young, R., Aung, T., Basit, A., ... Kelly, M. (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

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

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.",

author = "Kooner, {Jaspal S} and Danish Saleheen and Xueling Sim and Joban Sehmi and Weihua Zhang and Philippe Frossard and Been, {Latonya F} and Kee-Seng Chia and Dimas, {Antigone S} and Neelam Hassanali and Tazeen Jafar and Jowett, {Jeremy B M} and Xinzhong Li and Venkatesan Radha and Rees, {Simon D} and Fumihiko Takeuchi and Robin Young and Tin Aung and Abdul Basit and Manickam Chidambaram and Debashish Das and Elin Grundberg and Hedman, {Asa K} and Hydrie, {Zafar I} and Muhammed Islam and Chiea-Chuen Khor and Sudhir Kowlessur and Kristensen, {Malene M} and Samuel Liju and Wei-Yen Lim and Matthews, {David R} and Jianjun Liu and Morris, {Andrew P} and Nica, {Alexandra C} and Pinidiyapathirage, {Janani M} and Inga Prokopenko and Asif Rasheed and Maria Samuel and Nabi Shah and Shera, {A Samad} and Small, {Kerrin S} and Chen Suo and Wickremasinghe, {Ananda R} and Wong, {Tien Yin} and Mingyu Yang and Fan Zhang and Abecasis, {Goncalo R} and Barnett, {Anthony H} and Mark Caulfield and {DIAGRAM Consortium} and Marilyn Kelly",

year = "2011",

month = aug,

day = "28",

doi = "10.1038/ng.921",

language = "English",

volume = "43",

pages = "984--989",

journal = "Nature Genetics",

issn = "1546-1718",

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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, DIAGRAM Consortium & Kelly, M 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

TY - JOUR

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

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 - DIAGRAM Consortium

AU - Kelly, Marilyn

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.

U2 - 10.1038/ng.921

DO - 10.1038/ng.921

M3 - Article

C2 - 21874001

SN - 1546-1718

VL - 43

SP - 984

EP - 989

JO - Nature Genetics

JF - Nature Genetics

IS - 10

ER -

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

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