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
