Genome-wide association study for type 2 diabetes in indians identifies a new susceptibility locus at 2q21

Rubina Tabassum, Ganesh Chauhan, Om Prakash Dwivedi, Anubha Mahajan, Alok Jaiswal, Ismeet Kaur, Khushdeep Bandesh, Tejbir Singh, Benan John Mathai, Yogesh Pandey, Manickam Chidambaram, Amitabh Sharma, Sreenivas Chavali, Shantanu Sengupta, Lakshmi Ramakrishnan, Pradeep Venkatesh, Sanjay K. Aggarwal, Saurabh Ghosh, Dorairaj Prabhakaran, Reddy K. SrinathMadhukar Saxena, Monisha Banerjee, Sandeep Mathur, Anil Bhansali, Viral N. Shah, Sri Venkata Madhu, Raman K. Marwaha, Analabha Basu, Vinod Scaria, Mark I. McCarthy, Radha Venkatesan, Viswanathan Mohan, Nikhil Tandon, Dwaipayan Bharadwaj

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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 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 the same across populations, but also reveals a population- specific locus and provides further insights into genetic architecture and etiology of T2D.

Original languageEnglish
Pages (from-to)977-986
Number of pages10
JournalDiabetes
Volume62
Issue number3
DOIs
Publication statusPublished - 1 Mar 2013

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ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Tabassum, R., Chauhan, G., Dwivedi, O. P., Mahajan, A., Jaiswal, A., Kaur, I., Bandesh, K., Singh, T., Mathai, B. J., Pandey, Y., Chidambaram, M., Sharma, A., Chavali, S., Sengupta, S., Ramakrishnan, L., Venkatesh, P., Aggarwal, S. K., Ghosh, S., Prabhakaran, D., ... Bharadwaj, D. (2013). Genome-wide association study for type 2 diabetes in indians identifies a new susceptibility locus at 2q21. Diabetes, 62(3), 977-986. https://doi.org/10.2337/db12-0406