title: Variants in KCNQ1 are associated with susceptibility to type 2 diabetes mellitus.
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.
authors: Department of Metabolic Disorder, Research Institute, International Medical Center of Japan, Tokyo 162-8655, Japan.
authors: Kazuki
authors: K
authors: Yasuda
authors: Kazuaki
authors: K
authors: Miyake
authors: Yukio
authors: Y
authors: Horikawa
authors: Kazuo
authors: K
authors: Hara
authors: Haruhiko
authors: H
authors: Osawa
authors: Hiroto
authors: H
authors: Furuta
authors: Yushi
authors: Y
authors: Hirota
authors: Hiroyuki
authors: H
authors: Mori
authors: Anna
authors: A
authors: Jonsson
authors: Yoshifumi
authors: Y
authors: Sato
authors: Kazuya
authors: K
authors: Yamagata
authors: Yoshinori
authors: Y
authors: Hinokio
authors: He-Yao
authors: HY
authors: Wang
authors: Toshihito
authors: T
authors: Tanahashi
authors: Naoto
authors: N
authors: Nakamura
authors: Yoshitomo
authors: Y
authors: Oka
authors: Naoko
authors: N
authors: Iwasaki
authors: Yasuhiko
authors: Y
authors: Iwamoto
authors: Yuichiro
authors: Y
authors: Yamada
authors: Yutaka
authors: Y
authors: Seino
authors: Hiroshi
authors: H
authors: Maegawa
authors: Atsunori
authors: A
authors: Kashiwagi
authors: Jun
authors: J
authors: Takeda
authors: Eiichi
authors: E
authors: Maeda
authors: Hyoung Doo
authors: HD
authors: Shin
authors: Young Min
authors: YM
authors: Cho
authors: Kyong Soo
authors: KS
authors: Park
authors: Hong Kyu
authors: HK
authors: Lee
authors: Maggie C Y
authors: MC
authors: Ng
authors: Ronald C W
authors: RC
authors: Ma
authors: Wing-Yee
authors: WY
authors: So
authors: Juliana C N
authors: JC
authors: Chan
authors: Valeriya
authors: V
authors: Lyssenko
authors: Tiinamaija
authors: T
authors: Tuomi
authors: Peter
authors: P
authors: Nilsson
authors: Leif
authors: L
authors: Groop
authors: Naoyuki
authors: N
authors: Kamatani
authors: Akihiro
authors: A
authors: Sekine
authors: Yusuke
authors: Y
authors: Nakamura
authors: Ken
authors: K
authors: Yamamoto
authors: Teruhiko
authors: T
authors: Yoshida
authors: Katsushi
authors: K
authors: Tokunaga
authors: Mitsuo
authors: M
authors: Itakura
authors: Hideichi
authors: H
authors: Makino
authors: Kishio
authors: K
authors: Nanjo
authors: Takashi
authors: T
authors: Kadowaki
authors: Masato
authors: M
authors: Kasuga
mesh_terms: D044466:Asian People / Q000235:genetics; D002874:Chromosome Mapping; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D050417:Insulin-Secreting Cells / Q000502:physiology; D051657:KCNQ1 Potassium Channel / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D044465:White People
chemical_list: D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human