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Variants in KCNQ1 are associated with susceptibility to type 2 diabetes mellitus

Cited 541 time in Web of Science Cited 563 time in Scopus
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; Maegawa, Hiroshi; Kashiwagi, Atsunori; Takeda, Jun; Maeda, Eiichi; Shin, Hyoung Doo; Cho, Young Min; Park, Kyong Soo; Lee, Hong Kyu; Ng, Maggie C Y; Ma, Ronald C W; So, Wing-Yee; Chan, Juliana C N; Lyssenko, Valeriya; Tuomi, Tiinamaija; Nilsson, Peter; Groop, Leif; Kamatani, Naoyuki; Sekine, Akihiro; Nakamura, Yusuke; Yamamoto, Ken; Yoshida, Teruhiko; Tokunaga, Katsushi; Itakura, Mitsuo; Makino, Hideichi; Nanjo, Kishio; Kadowaki, Takashi; Kasuga, Masato
Issue Date
2008-08-20
Publisher
Nature Publishing Group
Citation
Nat Genet. 2008 ;40(9):1092-7.
Keywords
Asian Continental Ancestry Group/geneticsChromosome MappingDiabetes Mellitus, Type 2/*geneticsEuropean Continental Ancestry GroupGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansInsulin-Secreting Cells/physiologyKCNQ1 Potassium Channel/*genetics*Polymorphism, Single Nucleotide
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 Pvalue (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.
ISSN
1061-4036 (Print)
Language
English
URI
https://hdl.handle.net/10371/62252
DOI
https://doi.org/10.1038/ng.207
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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