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TABASSUM, Rubina; CHAUHAN, Ganesh; CHIDAMBARAM, Manickam; SHARMA, Amitabh; CHAVALI, Sreenivas; SENGUPTA, Shantanu; RAMAKRISHNAN, Lakshmi; VENKATESH, Pradeep; AGGARWAL, Sanjay K; GHOSH, Saurabh; PRABHAKARAN, Dorairaj; SRINATH, Reddy K; OM PRAKASH DWIVEDI; SAXENA, Madhukar; BANERJEE, Monisha; MATHUR, Sandeep; BHANSALI, Anil; SHAH, Viral N; SRI VENKATA MADHU; MARWAHA, Raman K; BASU, Analabha; SCARIA, Vinod; MCCARTHY, Mark I; MAHAJAN, Anubha; VENKATESAN, Radha; MOHAN, Viswanathan; TANDON, Nikhil; BHARADWAJ, Dwaipayan; JAISWAL, Alok; KAUR, Ismeet; BANDESH, Khushdeep; SINGH, Tejbir; BENAN JOHN MATHAI; PANDEY, Yogesh
Diabetes (New York, N.Y.), 03/2013, Letnik: 62, Številka: 3Journal Article
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.
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