Variants in KCNQ1 are associated with susceptibility to type 2 diabetes mellitus.
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.
Yasuda
Kazuki
K
Department of Metabolic Disorder, Research Institute, International Medical Center of Japan, Tokyo 162-8655, Japan.
Miyake
Kazuaki
K
Horikawa
Yukio
Y
Hara
Kazuo
K
Osawa
Haruhiko
H
Furuta
Hiroto
H
Hirota
Yushi
Y
Mori
Hiroyuki
H
Jonsson
Anna
A
Sato
Yoshifumi
Y
Yamagata
Kazuya
K
Hinokio
Yoshinori
Y
Wang
He-Yao
HY
Tanahashi
Toshihito
T
Nakamura
Naoto
N
Oka
Yoshitomo
Y
Iwasaki
Naoko
N
Iwamoto
Yasuhiko
Y
Yamada
Yuichiro
Y
Seino
Yutaka
Y
Maegawa
Hiroshi
H
Kashiwagi
Atsunori
A
Takeda
Jun
J
Maeda
Eiichi
E
Shin
Hyoung Doo
HD
Cho
Young Min
YM
Park
Kyong Soo
KS
Lee
Hong Kyu
HK
Ng
Maggie C Y
MC
Ma
Ronald C W
RC
So
Wing-Yee
WY
Chan
Juliana C N
JC
Lyssenko
Valeriya
V
Tuomi
Tiinamaija
T
Nilsson
Peter
P
Groop
Leif
L
Kamatani
Naoyuki
N
Sekine
Akihiro
A
Nakamura
Yusuke
Y
Yamamoto
Ken
K
Yoshida
Teruhiko
T
Tokunaga
Katsushi
K
Itakura
Mitsuo
M
Makino
Hideichi
H
Nanjo
Kishio
K
Kadowaki
Takashi
T
Kasuga
Masato
M
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
D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human