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SNPs in KCNQ1 are associated with susceptibility to type 2 diabetes in East Asian and European populations

Abstract

We conducted a genome-wide association study using 207,097 SNP markers in Japanese individuals with type 2 diabetes and unrelated controls, and identified KCNQ1 (potassium voltage-gated channel, KQT-like subfamily, member 1) to be a strong candidate for conferring susceptibility to type 2 diabetes. We detected consistent association of a SNP in KCNQ1 (rs2283228) with the disease in several independent case-control studies (additive model P = 3.1 × 10−12; OR = 1.26, 95% CI = 1.18–1.34). Several other SNPs in the same linkage disequilibrium (LD) block were strongly associated with type 2 diabetes (additive model: rs2237895, P = 7.3 × 10−9; OR = 1.32, 95% CI = 1.20–1.45, rs2237897, P = 6.8 × 10−13; OR = 1.41, 95% CI = 1.29–1.55). The association of these SNPs with type 2 diabetes was replicated in samples from Singaporean (additive model: rs2237895, P = 8.5 × 10−3; OR = 1.14, rs2237897, P = 2.4 × 10−4; OR = 1.22) and Danish populations (additive model: rs2237895, P = 3.7 × 10−11; OR = 1.24, rs2237897, P = 1.2 × 10−4; OR = 1.36).

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Figure 1: Schematic view of the association of type 2 diabetes with the variants in the KCNQ1 region.

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Acknowledgements

We thank all participating doctors and staff from collaborating institutes for providing DNA samples. We also thank the technical staff of the Laboratory for Endocrinology and Metabolism at the Center for Genomic Medicine for providing technical assistance. This work was partly supported by a grant from the Leading Project of Ministry of Education, Culture, Sports, Science and Technology Japan. The Danish study was supported by Lundbeck Foundation Centre of Applied Medical Genomics in Personalized Disease Prediction, Prevention and Care (LUCAMP), the European Union (EUGENE2, grant no. LSHM-CT-2004-512013) and the Danish Medical Research Council. Funding for Singapore arm of the study was supported by the National Medical Research Council (NMRC/1115/2007). We thank the staff of National Healthcare Group Polyclinics and National University of Singapore for their contributions towards the establishment of the Singapore Diabetes Cohort Study.

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Contributions

Principal investigators: S.M., H.U., Y.N. BioBank project planning and design: Y.N. Collected subjects and participated in the diagnostic evaluations: K.H., M. Horikoshi, T.B., H.H., M. Hayashi, Y.I., A.K., K.K., R. Kawamori, T. Kadowaki, R. Kikkawa. Oversaw a genotyping: M.K. Wrote the paper: S.M., H.U., Y.N., O.P. Statistical analyses: A.T., T. Kawaguchi, T.T., N.K. Principal investigator for Singapore study: D.P.K.N. Singapore study: S.N., E.S.T. Principal investigator for Danish study: O.P. Danish study: G.A., J.H., K.B.-J., T.J., A.S., T.L., T.H.

Corresponding author

Correspondence to Shiro Maeda.

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Supplementary Figures 1–4, Supplementary Tables 1–6 (PDF 2297 kb)

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Unoki, H., Takahashi, A., Kawaguchi, T. et al. SNPs in KCNQ1 are associated with susceptibility to type 2 diabetes in East Asian and European populations. Nat Genet 40, 1098–1102 (2008). https://doi.org/10.1038/ng.208

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