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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Kazuki Yasuda
  • Kazuaki Miyake
  • Yukio Horikawa
  • Kazuo Hara
  • Haruhiko Osawa
  • Hiroto Furuta
  • Yushi Hirota
  • Hiroyuki Mori
  • Yoshifumi Sato
  • Kazuya Yamagata
  • Yoshinori Hinokio
  • He-Yao Wang
  • Toshihito Tanahashi
  • Naoto Nakamura
  • Yoshitomo Oka
  • Naoko Iwasaki
  • Yasuhiko Iwamoto
  • Yuichiro Yamada
  • Yutaka Seino
  • Hiroshi Maegawa
  • Atsunori Kashiwagi
  • Jun Takeda
  • Eiichi Maeda
  • Hyoung Doo Shin
  • Young Min Cho
  • Kyong Soo Park
  • Hong Kyu Lee
  • Maggie C Y Ng
  • Ronald C W Ma
  • Wing-Yee So
  • Juliana C N Chan
  • Valeriya Lyssenko
  • Tiinamaija Tuomi
  • Peter Nilsson
  • Leif Groop
  • Naoyuki Kamatani
  • Akihiro Sekine
  • Yusuke Nakamura
  • Ken Yamamoto
  • Teruhiko Yoshida
  • Katsushi Tokunaga
  • Mitsuo Itakura
  • Hideichi Makino
  • Kishio Nanjo
  • Takashi Kadowaki
  • Masato Kasuga
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.
OriginalsprogEngelsk
TidsskriftNature Genetics
Vol/bind40
Udgave nummer9
Sider (fra-til)1092-7
Antal sider6
ISSN1061-4036
DOI
StatusUdgivet - sep. 2008

ID: 46404685