期刊
DIABETES
卷 62, 期 3, 页码 977-986出版社
AMER DIABETES ASSOC
DOI: 10.2337/db12-0406
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资金
- Council for Scientific and Industrial Research, Government of India [NWP0032-19]
- Fogarty International Center
- Eunice Kennedy Shriver National Institute of Child Health and Human Development at the National Institutes of Health [D43-11D-065249]
- MRC [MC_U127592696, MC_PC_U127592696] Funding Source: UKRI
- Medical Research Council [MC_PC_U127592696, MC_U127592696] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0611-10219] Funding Source: researchfish
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 X 10(-9)). Imputation analysis refined the signal to rs998451 (odds ratio 1.56; P = 6.3 x 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. Diabetes 62:977-986, 2013
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