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

Tabassum, R and Chauhan, G and Dwivedi, O P and Mahajan, A and Jaiswal, A and Kaur, I and Bandesh, K and Singh, T and Mathai, B J and Pandey, Y and Chidambaram, M and Sharma, A and Chavali, S and Sengupta, S and Ramakrishnan, L and Venkatesh, P and Aggarwal, S K and Ghosh, S and Prabhakaran, D and Srinath, R K and Saxena, M and Banerjee, M and Mathur, S and Bhansali, A and Shah, V N and Madhu, S V and Marwaha, R K and Basu, A and Scaria, V and McCarthy, M I and Venkatesan, R and Mohan, V and Tandon, N and Bharadwaj, D (2013) Genome-Wide Association Study for Type 2 Diabetes in Indians Identifies a New Susceptibility Locus at 2q21. Diabetes, 62 (3). p. 977. ISSN 0012-1797

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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 3 1029). Imputation analysis refined the signal to rs998451 (odds ratio 1.56; P = 6.3 3 10212) 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 same across populations, but also reveals a populationspecific locus and provides further insights into genetic architecture and etiology of T2D.

Item Type:Article
Official URL/DOI:
Uncontrolled Keywords:Diabetes; genome T2DM; Indians
Subjects:Genetics and Diabetes
Diabetology > Diabetes Mellitus Type 2
Divisions:Neonatal Diabetes
Department of Diabetology
ID Code:671
Deposited On:20 May 2013 10:12
Last Modified:20 May 2013 10:12

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