Journal Article

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

Emilsson, Valur, Adeyemo, Adebowale, Wijmenga, Cisca, Zhou, Jie, Thorleifsson, Gudmar, van Vliet-Ostaptchouk, Jana V, Baker, Adam, Gulcher, Jeffrey R, Chan, Juliana C N, Ma, Ronald C Y, Gudnason, Vilmundur, Thorsteinsdottir, Unnur, Ghosh, Shyamali, Bagger, Yu, Huang, Hanxia, Pedersen, Oluf, Andersen, Gitte, Borch-Johnsen, Knut, Steinthorsdottir, Valgerdur, Walters, G Bragi, Gurney, Mark, Doumatey, Ayo, Reynisdottir, Inga, Snorradottir, Steinunn, Christiansen, Claus, Wilensky, Robert L, Chen, Yuanxiu, So, Wing-Yee, Rotimi, Charles, Kong, Augustine, Reilly, Muredach P, Stefansson, Kari, Ng, Maggie C Y, Hofker, Marten H, Rader, Daniel J, Jonsdottir, Thorbjorg, Bjarnason, Hjordis, Styrkarsdottir, Unnur, Hansen, Torben, Jorgensen, Torben, Benediktsson, Rafn, Gretarsdottir, Solveig, Chen, Guanjie, Sigurdsson, Gunnar, Lashley, Kerrie

2007

Overview

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 × 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.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: Adult / Agriculture / Animal Genetics and Genomics / Biomedical and Life Sciences / Biomedicine / Blood Glucose - metabolism / Cancer Research / Carrier Proteins - genetics / Case-Control Studies / Comparative studies / Cross-Sectional Studies / Diabetes / Diabetes Mellitus, Type 2 - genetics / Female / Gene Frequency / Gene Function / Genes / Genetic aspects / Genetic markers / Genetic variation / Genome, Human / Genomics / Genotype & phenotype / Human Genetics / Humans / Identification and classification / Insulin / Insulin - metabolism / Insulin Resistance - genetics / Insulin Secretion / Intracellular Signaling Peptides and Proteins - genetics / letter / Linkage Disequilibrium / Male / Middle Aged / Nerve Tissue Proteins - genetics / Physiological aspects / Polymorphism, Single Nucleotide / Risk factors / TCF Transcription Factors - genetics / Transcription Factor 7-Like 1 Protein / Transcription Factor 7-Like 2 Protein / Type 2 diabetes