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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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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
ISSN (print) / ISBN 0012-1797
e-ISSN 1939-327X
Zeitschrift Diabetes
Quellenangaben Band: 62, Heft: 3, Seiten: 977-986 Artikelnummer: , Supplement: ,
Verlag American Diabetes Association
Verlagsort Alexandria, VA.
Begutachtungsstatus Peer reviewed