Genome-Wide Association Study for Type 2 Diabetes in Indians Identifies a New Susceptibility Locus at 2q21
- Rubina Tabassum1,
- Ganesh Chauhan1,
- Om Prakash Dwivedi1,
- Anubha Mahajan1,
- Alok Jaiswal1,
- Ismeet Kaur1,
- Khushdeep Bandesh1,
- Tejbir Singh1,
- Benan John Mathai1,
- Yogesh Pandey1,
- Manickam Chidambaram2,
- Amitabh Sharma1,
- Sreenivas Chavali1,
- Shantanu Sengupta1,
- Lakshmi Ramakrishnan3,
- Pradeep Venkatesh3,
- Sanjay K. Aggarwal3,
- Saurabh Ghosh4,
- Dorairaj Prabhakaran5,
- Reddy K. Srinath6,
- Madhukar Saxena7,
- Monisha Banerjee7,
- Sandeep Mathur8,
- Anil Bhansali9,
- Viral N. Shah9,
- Sri Venkata Madhu10,
- Raman K. Marwaha11,
- Analabha Basu12,
- Vinod Scaria13,
- Mark I. McCarthy14,15,16,
- Radha Venkatesan2,
- Viswanathan Mohan2,
- Nikhil Tandon3⇓ and
- Dwaipayan Bharadwaj1⇓
- 1Genomics and Molecular Medicine Unit, Council for Scientific and Industrial Research-Institute of Genomics and Integrative Biology, Delhi, India
- 2Department of Molecular Genetics, Madras Diabetes Research Foundation-Indian Council of Medical Research Advanced Centre for Genomics of Diabetes, Chennai, India
- 3Department of Endocrinology, All India Institute of Medical Sciences, New Delhi, India
- 4Human Genetics Unit, Indian Statistical Institute, Kolkata, India
- 5Centre for Chronic Disease Control, New Delhi, India
- 6Public Health Foundation of India, New Delhi, India
- 7Department of Zoology, University of Lucknow, Lucknow, India
- 8Department of Endocrinology, SMS Medical College and Hospital, Jaipur, India
- 9Department of Endocrinology, Post Graduate Institute of Medical Education and Research, Sector-12, Chandigarh, India
- 10Division of Endocrinology, University College of Medical Sciences, Delhi, India
- 11Department of Endocrinology and Thyroid Research, Institute of Nuclear Medicine and Allied Sciences, Delhi, India
- 12National Institute of BioMedical Genomics, Kalyani, India
- 13GN Ramachandran Knowledge Center for Genome Informatics, Council for Scientific and Industrial Research-Institute of Genomics and Integrative Biology, Delhi, India
- 14Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom
- 15Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, United Kingdom
- 16Oxford National Institute for Health Research Biomedical Research Centre, Churchill Hospital, Oxford, United Kingdom
- Corresponding authors: Dwaipayan Bharadwaj, , and Nikhil Tandon, .
R.T., G.C., and O.P.D. contributed equally to this study.
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.
This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db12-0406/-/DC1.
* A complete list of the members of the DIAGRAM and INDICO consortia can be found in the Supplementary Data online.
- Received April 3, 2012.
- Accepted August 28, 2012.
- © 2013 by the American Diabetes Association.
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