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

Yasuda, Kazuki; Miyake, Kazuaki; Horikawa, Yukio; Hara, Kazuo; Osawa, Haruhiko; Furuta, Hiroto; Hirota, Yushi; Mori, Hiroyuki; Jonsson, Anna LU and Sato, Yoshifumi, et al. (2008) In Nature Genetics 40(9). p.1092-1097
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 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... (More)
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. (Less)
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type
Contribution to journal
publication status
published
subject
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Nature Genetics
volume
40
issue
9
pages
1092 - 1097
publisher
Nature Publishing Group
external identifiers
  • wos:000258761200022
  • scopus:50449085998
ISSN
1546-1718
DOI
10.1038/ng.207
language
English
LU publication?
yes
id
8136b84a-aae5-4a18-9c20-496bd86a56a4 (old id 1247658)
date added to LUP
2008-11-10 11:47:51
date last changed
2017-11-12 03:35:32
@article{8136b84a-aae5-4a18-9c20-496bd86a56a4,
  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 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.},
  author       = {Yasuda, Kazuki and Miyake, Kazuaki and Horikawa, Yukio and Hara, Kazuo and Osawa, Haruhiko and Furuta, Hiroto and Hirota, Yushi and Mori, Hiroyuki and Jonsson, Anna and Sato, Yoshifumi and Yamagata, Kazuya and Hinokio, Yoshinori and Wang, He-Yao and Tanahashi, Toshihito and Nakamura, Naoto and Oka, Yoshitomo and Iwasaki, Naoko and Iwamoto, Yasuhiko and Yamada, Yuichiro and Seino, Yutaka and Maegawa, Hiroshi and Kashiwagi, Atsunori and Takeda, Jun and Maeda, Eiichi and Shin, Hyoung Doo and Cho, Young Min and Park, Kyong Soo and Lee, Hong Kyu and Ng, Maggie C. Y. and Ma, Ronald C. W. and So, Wing-Yee and Chan, Juliana C. N. and Lyssenko, Valeriya and Tuomi, Tiinamaija and Nilsson, Peter and Groop, Leif and Kamatani, Naoyuki and Sekine, Akihiro and Nakamura, Yusuke and Yamamoto, Ken and Yoshida, Teruhiko and Tokunaga, Katsushi and Itakura, Mitsuo and Makino, Hideichi and Nanjo, Kishio and Kadowaki, Takashi and Kasuga, Masato},
  issn         = {1546-1718},
  language     = {eng},
  number       = {9},
  pages        = {1092--1097},
  publisher    = {Nature Publishing Group},
  series       = {Nature Genetics},
  title        = {Variants in KCNQ1 are associated with susceptibility to type 2 diabetes mellitus},
  url          = {http://dx.doi.org/10.1038/ng.207},
  volume       = {40},
  year         = {2008},
}