Genome-Wide Association Study for Type 2 Diabetes in Indians Identifies a New Susceptibility Locus at 2q21

  1. Dwaipayan Bharadwaj1
  1. 1Genomics and Molecular Medicine Unit, Council for Scientific and Industrial Research-Institute of Genomics and Integrative Biology, Delhi, India
  2. 2Department of Molecular Genetics, Madras Diabetes Research Foundation-Indian Council of Medical Research Advanced Centre for Genomics of Diabetes, Chennai, India
  3. 3Department of Endocrinology, All India Institute of Medical Sciences, New Delhi, India
  4. 4Human Genetics Unit, Indian Statistical Institute, Kolkata, India
  5. 5Centre for Chronic Disease Control, New Delhi, India
  6. 6Public Health Foundation of India, New Delhi, India
  7. 7Department of Zoology, University of Lucknow, Lucknow, India
  8. 8Department of Endocrinology, SMS Medical College and Hospital, Jaipur, India
  9. 9Department of Endocrinology, Post Graduate Institute of Medical Education and Research, Sector-12, Chandigarh, India
  10. 10Division of Endocrinology, University College of Medical Sciences, Delhi, India
  11. 11Department of Endocrinology and Thyroid Research, Institute of Nuclear Medicine and Allied Sciences, Delhi, India
  12. 12National Institute of BioMedical Genomics, Kalyani, India
  13. 13GN Ramachandran Knowledge Center for Genome Informatics, Council for Scientific and Industrial Research-Institute of Genomics and Integrative Biology, Delhi, India
  14. 14Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom
  15. 15Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, United Kingdom
  16. 16Oxford National Institute for Health Research Biomedical Research Centre, Churchill Hospital, Oxford, United Kingdom
  1. Corresponding authors: Dwaipayan Bharadwaj, db{at}igib.res.in, and Nikhil Tandon, nikhil_tandon{at}hotmail.com.
  1. R.T., G.C., and O.P.D. contributed equally to this study.

Abstract

Indians undergoing socioeconomic and lifestyle transitions will be maximally affected by epidemic of type 2 diabetes (T2D). We conducted a two-stage genome-wide association study of T2D in 12,535 Indians, a less explored but high-risk group. We identified a new type 2 diabetes–associated locus at 2q21, with the lead signal being rs6723108 (odds ratio 1.31; P = 3.32 × 10−9). Imputation analysis refined the signal to rs998451 (odds ratio 1.56; P = 6.3 × 10−12) within TMEM163 that encodes a probable vesicular transporter in nerve terminals. TMEM163 variants also showed association with decreased fasting plasma insulin and homeostatic model assessment of insulin resistance, indicating a plausible effect through impaired insulin secretion. The 2q21 region also harbors RAB3GAP1 and ACMSD; those are involved in neurologic disorders. Forty-nine of 56 previously reported signals showed consistency in direction with similar effect sizes in Indians and previous studies, and 25 of them were also associated (P < 0.05). Known loci and the newly identified 2q21 locus altogether explained 7.65% variance in the risk of T2D in Indians. Our study suggests that common susceptibility variants for T2D are largely the same across populations, but also reveals a population-specific locus and provides further insights into genetic architecture and etiology of T2D.

Footnotes

  • Received April 3, 2012.
  • Accepted August 28, 2012.

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  1. Diabetes vol. 62 no. 3 977-986
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