A variant in CDKAL1 influences insulin response and risk of type 2 diabetes
- Steinthorsdottir, V.
- Thorleifsson, G.
- Reynisdottir, I.
- Benediktsson, R.
- Jonsdottir, T.
- Walters, G.B.
- Styrkarsdottir, U.
- Gretarsdottir, S.
- Emilsson, V.
- Ghosh, S.
- Baker, A.
- Snorradottir, S.
- Bjarnason, H.
- Ng, M.C.
- Hansen, T.
- Bagger, Y.
- Wilensky, R.L.
- Reilly, M.P.
- Adeyemo, A.
- Chen, Y.
- Zhou, J.
- Gudnason, V.
- Chen, G.
- Huang, H.
- Lashley, K.
- Doumatey, A.
- So, W.Y.
- Ma, R.C.
- Andersen, G.
- Borch Johnsen, K.
- Jorgensen, T.
- van Vliet-Ostaptchouk, J.V.
- Hofker, M.H.
- Wijmenga, C.
- Christiansen, C.
- Rader, D.J.
- Rotimi, C.
- Gurney, M.
- Chan, J.C.
- Pedersen, O.
- Sigurdsson, G.
- Gulcher, J.R.
- Thorsteinsdottir, U.
- Kong, A.
- Stefansson, K.
DOIAbstract
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...
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