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).

1. Laboratory for Endocrinology and Metabolism, Center for Genomic Medicine, RIKEN, Yokohama, Kanagawa 230-0045, Japan.
2. Laboratory for Statistical Analysis, Center for Genomic Medicine, RIKEN, Yokohama, Kanagawa 230-0045, Japan.
3. Laboratory for Medical Informatics, Center for Genomic Medicine, RIKEN, Yokohama, Kanagawa 230-0045, Japan.
4. Department of Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.
5. Steno Diabetes Center, Niels Steensens Vej 2, DK-2820 Gentofte, Copenhagen, Denmark.
6. Department of Community, Occupational and Family Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore.
7. Research Centre for Prevention and Health, Glostrup University Hospital, 2600 Glostrup, Denmark.
8. Faculty of Health Science, University of Aarhus, 8000 Aarhus, Denmark.
9. Department of General Practice, University of Aarhus, 8000 Aarhus, Denmark.
10. Laboratory for Genotyping Development, Center for Genomic Medicine, RIKEN, Yokohama, Kanagawa 230-0045, Japan.
11. Diabetes Center, Tokyo Women's Medical University, Tokyo 162-8666, Japan.
12. Health Center, Keio University School of Medicine, Tokyo 160-8582, Japan.
13. Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan.
14. Department of Medicine, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan.
15. Division of Endocrinology and Metabolism, Department of Internal Medicine, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan.
16. Department of Medicine, Metabolism and Endocrinology, School of Medicine, Juntendo University, Tokyo 113-8421, Japan.
17. Department of Endocrinology, Singapore General Hospital, Singapore 169608, Singapore.
18. Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.

Correspondence to: Shiro Maeda¹ e-mail: smaeda@src.riken.jp

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