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Genome-Wide Association Study for Type 2 Diabetes in Indians Identifies a New Susceptibility Locus at 2q21
- Source :
- Diabetes, Diabetes 62, 977-986 (2013)
- Publication Year :
- 2013
- Publisher :
- American Diabetes Association, 2013.
-
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 × 10−9). 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.
- Subjects :
- Endocrinology, Diabetes and Metabolism
India
Nerve Tissue Proteins
030209 endocrinology & metabolism
Locus (genetics)
Genome-wide association study
Type 2 diabetes
Biology
Polymorphism, Single Nucleotide
White People
03 medical and health sciences
0302 clinical medicine
Insulin resistance
Asian People
Diabetes mellitus
Internal Medicine
medicine
Humans
Genetic Predisposition to Disease
Aged
030304 developmental biology
Genetics
0303 health sciences
Membrane Proteins
Genetics/Genomes/Proteomics/Metabolomics
Odds ratio
Middle Aged
medicine.disease
3. Good health
Diabetes Mellitus, Type 2
Genetic Loci
Chromosomes, Human, Pair 2
Homeostatic model assessment
Insulin Resistance
Imputation (genetics)
Genome-Wide Association Study
Subjects
Details
- ISSN :
- 1939327X and 00121797
- Volume :
- 62
- Database :
- OpenAIRE
- Journal :
- Diabetes
- Accession number :
- edsair.doi.dedup.....7e8866bc5e4e1eb8bf7e073f5c3fddea