Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2011 Aug 28;43(10):984-9.
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  1 , 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; DIAGRAM; MuTHER; 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
Affiliations

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

Jaspal S Kooner et al. Nat Genet. .

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.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Summary of study design
Figure 2
Figure 2
Manhattan plot for the primary South Asian genome-wide association analysis. of men and women, using directly genotyped SNPs. At the six novel loci reaching genome wide-significance, the sentinel SNPs are indicated: green dot for GWA result, and red dot for combined analysis of GWA and replication data in South Asians.
Figure 3
Figure 3
Regional plots for the six loci associated with type-2 diabetes in South Asians. (A) GRB14 region, (B) ST6GAL1 region, (C) VPS26A region, (D) HMG20A region, (E) AP3S2 region and (F) HNF4A region. Sentinel SNP: purple circle for genome-wide result; purple diamond for combined analysis with replication studies. Other genotyped SNPs colour coded according to pairwise LD with sentinel SNP, calculated in a representative sample of 83 South Asians from the Singapore Genome Variation Project. Recombination rates estimated from Hapmap Phase II combined panels. Regional plots also incorporating SNPs imputed from HapMap2 are shown in Supplementary Figures 7 and 8.
See this image and copyright information in PMC

References

    1. Chambers JC, Obeid OA, Refsum H, et al. Plasma homocysteine concentrations and risk of coronary heart disease in UK Indian Asian and European men. Lancet. 2000;355(9203):523–527. - PubMed
    1. Ramachandran A, Ma RC, Snehalatha C. Diabetes in Asia. Lancet. 2010;375(9712):408–418. - PubMed
    1. Shaw JE, Sicree RA, Zimmet PZ. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract. 2010;87(1):4–14. - PubMed
    1. McCarthy MI. Genomics, type 2 diabetes, and obesity. N Engl J Med. 2010;363:2339–50. - PubMed
    1. Jowett JB, Diego VP, Kotea N, et al. Genetic influences on type 2 diabetes and metabolic syndrome related quantitative traits in Mauritius. Twin Res Hum Genet. 2009;12(1):44–52. - PMC - PubMed

Publication types