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- Title
Variants in KCNQ1 are associated with susceptibility to type 2 diabetes mellitus.
- Authors
Yasuda, Kazuki; Miyake, Kazuaki; Horikawa, Yukio; Hara, Kazuo; Osawa, Haruhiko; Furuta, Hiroto; Hirota, Yushi; Mori, Hiroyuki; Jonsson, Anna; Sato, Yoshifumi; Yamagata, Kazuya; Hinokio, Yoshinori; Wang, He-Yao; Tanahashi, Toshihito; Nakamura, Naoto; Oka, Yoshitomo; Iwasaki, Naoko; Iwamoto, Yasuhiko; Yamada, Yuichiro; Seino, Yutaka
- Abstract
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 × 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 × 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 β-cell function or the corrected insulin response. Our data thus implicate KCNQ1 as a diabetes susceptibility gene in groups of different ancestries.
- Subjects
JAPAN; TYPE 2 diabetes; GENETIC polymorphisms; ENDOCRINE diseases; DIABETES; SAMPLING (Process)
- Publication
Nature Genetics, 2008, Vol 40, Issue 9, p1092
- ISSN
1061-4036
- Publication type
Article
- DOI
10.1038/ng.207