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Tabassum, R.* ; Chauhan, G.* ; Dwivedi, O.P.* ; Mahajan, A.* ; Jaiswal, A.* ; Kaur, I.* ; Bandesh, K.* ; Singh, T.* ; Mathai, B.J.* ; Pandey, Y.* ; Chidambaram, M.* ; Sharma, A.* ; Chavali, S.* ; Sengupta, S.* ; Ramakrishnan, L.* ; Venkatesh, P.* ; Aggarwal, S.K.* ; Ghosh, S.* ; Prabhakaran, D.* ; Srinath, R.K.* ; Saxena, M.* ; Banerjee, M.* ; Mathur, S.* ; Bhansali, A.* ; Shah, V.N.* ; Madhu, S.V.* ; Marwaha, R.K.* ; Basu, A.* ; Scaria, V.* ; McCarthy, M.I.* ; DIAGRAM Consortium (Gieger, C. ; Grallert, H. ; Huth, C. ; Illig, T. ; Klopp, N. ; Meitinger, T. ; Petersen, A.-K. ; Thorand, B. ; Wichmann, H.-E.) ; INDICO Consortium (*) ; Venkatesan, R.* ; Mohan, V.* ; Tandon, N.* ; Bharadwaj, D.*

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

Diabetes 62, 977-986 (2013)
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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.
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Publication type Article: Journal article
Document type Scientific Article
Language english
Publication Year 2013
HGF-reported in Year 2013
ISSN (print) / ISBN 0012-1797
e-ISSN 1939-327X
Journal Diabetes
Quellenangaben Volume: 62, Issue: 3, Pages: 977-986 Article Number: , Supplement: ,
Publisher American Diabetes Association
Publishing Place Alexandria, VA.
Reviewing status Peer reviewed
Institute(s) Research Unit Molecular Epidemiology (AME)
Institute of Genetic Epidemiology (IGE)
German Center for Diabetes Reseach (DZD)
Institute of Epidemiology (EPI)
POF-Topic(s) 30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
90000 - German Center for Diabetes Research
30202 - Environmental Health
Research field(s) Genetics and Epidemiology
PSP Element(s) G-504200-002
G-504100-001
G-501900-421
G-504000-002
G-501900-401
G-503900-002
PubMed ID 23209189
DOI 10.2337/db12-0406
Erfassungsdatum 2013-03-04
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