| Literature DB >> 17460697 |
Valgerdur Steinthorsdottir1, Gudmar Thorleifsson, Inga Reynisdottir, Rafn Benediktsson, Thorbjorg Jonsdottir, G Bragi Walters, Unnur Styrkarsdottir, Solveig Gretarsdottir, Valur Emilsson, Shyamali Ghosh, Adam Baker, Steinunn Snorradottir, Hjordis Bjarnason, Maggie C Y Ng, Torben Hansen, Yu Bagger, Robert L Wilensky, Muredach P Reilly, Adebowale Adeyemo, Yuanxiu Chen, Jie Zhou, Vilmundur Gudnason, Guanjie Chen, Hanxia Huang, Kerrie Lashley, Ayo Doumatey, Wing-Yee So, Ronald C Y Ma, Gitte Andersen, Knut Borch-Johnsen, Torben Jorgensen, Jana V van Vliet-Ostaptchouk, Marten H Hofker, Cisca Wijmenga, Claus Christiansen, Daniel J Rader, Charles Rotimi, Mark Gurney, Juliana C N Chan, Oluf Pedersen, Gunnar Sigurdsson, Jeffrey R Gulcher, Unnur Thorsteinsdottir, Augustine Kong, Kari Stefansson.
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.Entities:
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Year: 2007 PMID： 17460697 DOI： 10.1038/ng2043
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330