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

Valgerdur Steinthorsdottir*, 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 ChenJie 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

*Corresponding author af dette arbejde

    Publikation: Bidrag til tidsskriftArtikelForskningpeer review

    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 × 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.

    OriginalsprogEngelsk
    Sider (fra-til)770-775
    Antal sider6
    TidsskriftNature Genetics
    Vol/bind39
    Udgave nummer6
    DOI
    StatusUdgivet - 1 jun. 2007

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