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

DIAGRAM, Jaspal S. Kooner (Lead / Corresponding author), 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 BasitManickam 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, Panos Deloukas, Timothy M. Frayling, Philippe Froguel, Norihiro Kato, Prasad Katulanda, Ann M. 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 journalArticlepeer-review

352 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 - 28 Aug 2011

Keywords

  • Asian Continental Ancestry Group/genetics
  • Case-Control Studies
  • Diabetes Mellitus, Type 2/genetics
  • Female
  • Gene Expression Regulation
  • Genetic Predisposition to Disease
  • Genetics, Population
  • Genome, Human
  • Genome-Wide Association Study
  • Humans
  • Linkage Disequilibrium
  • London
  • Male
  • Pakistan
  • Polymorphism, Single Nucleotide
  • Quantitative Trait Loci
  • Singapore

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