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A variant in CDKAL1 influences insulin response and risk of type 2 diabetes.

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Authors
Steinthorsdottir, Valgerdur
Thorleifsson, Gudmar
Reynisdottir, Inga
Benediktsson, Rafn
Jonsdottir, Thorbjorg
Walters, G Bragi
Styrkarsdottir, Unnur
Gretarsdottir, Solveig
Emilsson, Valur
Ghosh, Shyamali
Baker, Adam
Snorradottir, Steinunn
Bjarnason, Hjordis
Ng, Maggie C Y
Hansen, Torben
Bagger, Yu
Wilensky, Robert L
Reilly, Muredach P
Adeyemo, Adebowale
Chen, Yuanxiu
Zhou, Jie
Gudnason, Vilmundur
Chen, Guanjie
Huang, Hanxia
Lashley, Kerrie
Doumatey, Ayo
So, Wing-Yee
Ma, Ronald C Y
Andersen, Gitte
Borch-Johnsen, Knut
Jorgensen, Torben
van Vliet-Ostaptchouk, Jana V
Hofker, Marten H
Wijmenga, Cisca
Christiansen, Claus
Rader, Daniel J
Rotimi, Charles
Gurney, Mark
Chan, Juliana C N
Pedersen, Oluf
Sigurdsson, Gunnar
Gulcher, Jeffrey R
Thorsteinsdottir, Unnur
Kong, Augustine
Stefansson, Kari
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Issue Date
2007-06-01

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Citation
Nat. Genet. 2007, 39(6):770-5
Abstract
We conducted a genome-wide association study for type 2 diabetes (T2D) in Icelandic cases and controls, and we found that a previously described variant in the transcription factor 7-like 2 gene (TCF7L2) gene conferred the most significant risk. In addition to confirming two recently identified risk variants, we identified a variant in the CDKAL1 gene that was associated with T2D in individuals of European ancestry (allele-specific odds ratio (OR) = 1.20 (95% confidence interval, 1.13-1.27), P = 7.7 x 10(-9)) and individuals from Hong Kong of Han Chinese ancestry (OR = 1.25 (1.11-1.40), P = 0.00018). The genotype OR of this variant suggested that the effect was substantially stronger in homozygous carriers than in heterozygous carriers. The ORs for homozygotes were 1.50 (1.31-1.72) and 1.55 (1.23-1.95) in the European and Hong Kong groups, respectively. The insulin response for homozygotes was approximately 20% lower than for heterozygotes or noncarriers, suggesting that this variant confers risk of T2D through reduced insulin secretion.
Description
To access publisher full text version of this article. Please click on the hyperlink in Additional Link
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http://www.nature.com/ng/journal/v39/n6/full/ng2043.html
ae974a485f413a2113503eed53cd6c53
10.1038/ng2043
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English Journal Articles (Peer Reviewed)

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