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- Title
A variant in CDKAL1 influences insulin response and risk of type 2 diabetes.
- 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
- 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.
- Publication
Nature genetics, 2007, Vol 39, Issue 6, p770
- ISSN
1061-4036
- Publication type
Journal Article
- DOI
10.1038/ng2043