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

Article


Kooner, Jaspal S., Saleheem, 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 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. https://doi.org/10.1038/ng.921
Article Title

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

ERA Journal ID16629
Article CategoryArticle
AuthorsKooner, Jaspal S. (Author), Saleheem, Danish (Author), Sim, Xueling (Author), Sehmi, Joban (Author), Zhang, Weihua (Author), Frossard, Philippe (Author), Been, Latonya F. (Author), Chia, Kee-Seng (Author), Dimas, Antigone S. (Author), Hassanali, Neelam (Author), Jafar, Tazeen (Author), Jowett, Jeremy B. M. (Author), Li, Xinzhong (Author), Radha, Venkatesan (Author), Rees, Simon D. (Author), Takeuchi, Fumihiko (Author), Young, Robin (Author) and Pinidiyapathirage, Janani M. (Author)
Journal TitleNature Genetics
Journal Citation43 (10), pp. 984-989
Number of Pages17
Year2011
Place of PublicationUnited States
ISSN1061-4036
1546-1718
Digital Object Identifier (DOI)https://doi.org/10.1038/ng.921
Web Address (URL)https://www.nature.com/articles/ng.921
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.

Keywordsadult; 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
Contains Sensitive ContentDoes not contain sensitive content
ANZSRC Field of Research 2020320208. Endocrinology
310509. Genomics
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Institution of OriginUniversity of Southern Queensland
Byline AffiliationsImperial College London, United Kingdom
University of Cambridge, United Kingdom
National University of Singapore
Center for Non-Communicable Diseases, Pakistan
University of Oklahoma, United States
University of Geneva, Switzerland
University of Oxford, United Kingdom
Aga Khan University, Pakistan
Baker Heart and Diabetes Institute, Australia
Madras Diabetes Research Foundation, India
University of Birmingham, United Kingdom
National Center for Global Health and Medicine, Japan
University of Kelaniya, Sri Lanka
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