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


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??). 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.

SUBMITTER: Tabassum R 

PROVIDER: S-EPMC3581193 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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

Tabassum Rubina R   Chauhan Ganesh G   Dwivedi Om Prakash OP   Mahajan Anubha A   Jaiswal Alok A   Kaur Ismeet I   Bandesh Khushdeep K   Singh Tejbir T   Mathai Benan John BJ   Pandey Yogesh Y   Chidambaram Manickam M   Sharma Amitabh A   Chavali Sreenivas S   Sengupta Shantanu S   Ramakrishnan Lakshmi L   Venkatesh Pradeep P   Aggarwal Sanjay K SK   Ghosh Saurabh S   Prabhakaran Dorairaj D   Srinath Reddy K RK   Saxena Madhukar M   Banerjee Monisha M   Mathur Sandeep S   Bhansali Anil A   Shah Viral N VN   Madhu Sri Venkata SV   Marwaha Raman K RK   Basu Analabha A   Scaria Vinod V   McCarthy Mark I MI   Venkatesan Radha R   Mohan Viswanathan V   Tandon Nikhil N   Bharadwaj Dwaipayan D  

Diabetes 20121203 3


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 probabl  ...[more]

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