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

V. Steinthorsdottir, G. Thorleifsson, I. Reynisdottir, R. Benediktsson, T. Jonsdottir, G.B. Walters, U. Styrkarsdottir, S. Gretarsdottir, V. Emilsson, S. Ghosh, A. Baker, S. Snorradottir, H. Bjarnason, M.C. Ng, T. Hansen, Y. Bagger, R.L. Wilensky, M.P. Reilly, A. Adeyemo, Y. ChenJ. Zhou, V. Gudnason, G. Chen, H. Huang, K. Lashley, A. Doumatey, W.Y. So, R.C. Ma, G. Andersen, K. Borch-Johnsen, T. Jorgensen, J.V. van Vliet-Ostaptchouk, M.H. Hofker, C. Wijmenga, C. Christiansen, D.J. Rader, C. Rotimi, M. Gurney, J.C. Chan, O. Pedersen, G. Sigurdsson, J.R. Gulcher, U. Thorsteinsdottir, A. Kong, K. Stefansson

OnderzoeksoutputAcademicpeer review

900 Citaten (Scopus)
1117 Downloads (Pure)

Samenvatting

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(1), 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.

Originele taal-2English
Pagina's (van-tot)770-775
Aantal pagina's6
TijdschriftNature Genetics
Volume39
Nummer van het tijdschrift6
DOI's
StatusPublished - jun.-2007

Vingerafdruk

Duik in de onderzoeksthema's van 'A variant in CDKAL1 influences insulin response and risk of type 2 diabetes'. Samen vormen ze een unieke vingerafdruk.

Citeer dit