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

Kooner, Jaspal S. and Saleheem, Danish and Sim, Xueling and Sehmi, Joban and Zhang, Weihua and Frossard, Philippe and Been, Latonya F. and Chia, Kee-Seng and Dimas, Antigone S. and Hassanali, Neelam and Jafar, Tazeen and Jowett, Jeremy B. M. and Li, Xinzhong and Radha, Venkatesan and Rees, Simon D. and Takeuchi, Fumihiko and Young, Robin and Pinidiyapathirage, Janani M. (2011) Genome-wide association study in individuals of South Asian ancestry identifies six new type 2 diabetes susceptibility loci. Nature Genetics, 43 (10). pp. 984-989. ISSN 1061-4036

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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Item Type: Article (Commonwealth Reporting Category C)
Refereed: Yes
Item Status: Live Archive
Additional Information: Access to accepted version in accordance with the copyright policy of the publisher.
Faculty / Department / School: Current - Institute for Agriculture and the Environment
Date Deposited: 31 Aug 2016 23:45
Last Modified: 31 Jan 2017 03:53
Uncontrolled Keywords: adult; article; clinical article; controlled study; female; gene locus; gene replication; genetic association; genetic identification; genetic predisposition; genetic susceptibility; genome analysis; human; insulin sensitivity; male; non insulin dependent diabetes mellitus; Pakistan; pancreas islet beta cell; population genetics; priority journal; Singapore; single nucleotide polymorphism; South Asia; United Kingdom
Fields of Research : 11 Medical and Health Sciences > 1103 Clinical Sciences > 110306 Endocrinology
06 Biological Sciences > 0604 Genetics > 060408 Genomics
Socio-Economic Objective: E Expanding Knowledge > 97 Expanding Knowledge > 970111 Expanding Knowledge in the Medical and Health Sciences
Identification Number or DOI: 10.1038/ng.921
URI: http://eprints.usq.edu.au/id/eprint/29632

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