期刊
NATURE GENETICS
卷 40, 期 9, 页码 1092-1097出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.207
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资金
- Pharmaceuticals and Medical Devices Agency (PMDA) of Japan
- National Institute of Biomedical Innovation (NIBIO) of Japan
- Ministry of Health, Labour, and Welfare of Japan
- New Energy and Industrial Technology Development Organization (NEDO)
- Cooperative Link of Unique Science and Technology for Economy Revitalization (CLUSTER, Tokushima, Japan)
- Hong Kong Research Grants Committee Central Allocation Scheme [1/04C]
- Ministry of Health and Welfare of the Republic of Korea [00-PJ3-PG6-GN07-001]
- Swedish Research Council
- Sigrid Juselius Foundation
- Folkhaelsan Research Foundation
- European Foundation for the Study of Diabetes
- Swedish Diabetes Research Foundation
We carried out a multistage genome-wide association study of type 2 diabetes mellitus in Japanese individuals, with a total of 1,612 cases and 1,424 controls and 100,000 SNPs. The most significant association was obtained with SNPs in KCNQ1, and dense mapping within the gene revealed that rs2237892 in intron 15 showed the lowest P value (6.7 x 10(-13), odds ratio (OR) = 1.49). The association of KCNQ1 with type 2 diabetes was replicated in populations of Korean, Chinese and European ancestry as well as in two independent Japanese populations, and meta-analysis with a total of 19,930 individuals (9,569 cases and 10,361 controls) yielded a P value of 1.7 x 10(-42) (OR = 1.40; 95% CI = 1.34-1.47) for rs2237892. Among control subjects, the risk allele of this polymorphism was associated with impairment of insulin secretion according to the homeostasis model assessment of beta-cell function or the corrected insulin response. Our data thus implicate KCNQ1 as a diabetes susceptibility gene in groups of different ancestries.
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