Indians Identifies a New Susceptibility Locus at

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). Impu-tation 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 homeo-static model assessment of insulin resistance, indicating a plausi-ble effect through impaired insulin secretion. The 2q21 region also harbors RAB3GAP1 and ACMSD; those are involved in neu-rologic disorders. Forty-nine of 56 previously reported signals showed consistency in direction with similar effect sizes in Indi