SNPs in KCNQ1 are associated with susceptibility to type 2 diabetes in East Asian and European populations.
We conducted a genome-wide association study using 207,097 SNP markers in Japanese individuals with type 2 diabetes and unrelated controls, and identified KCNQ1 (potassium voltage-gated channel, KQT-like subfamily, member 1) to be a strong candidate for conferring susceptibility to type 2 diabetes. We detected consistent association of a SNP in KCNQ1 (rs2283228) with the disease in several independent case-control studies (additive model P = 3.1 x 10(-12); OR = 1.26, 95% CI = 1.18-1.34). Several other SNPs in the same linkage disequilibrium (LD) block were strongly associated with type 2 diabetes (additive model: rs2237895, P = 7.3 x 10(-9); OR = 1.32, 95% CI = 1.20-1.45, rs2237897, P = 6.8 x 10(-13); OR = 1.41, 95% CI = 1.29-1.55). The association of these SNPs with type 2 diabetes was replicated in samples from Singaporean (additive model: rs2237895, P = 8.5 x 10(-3); OR = 1.14, rs2237897, P = 2.4 x 10(-4); OR = 1.22) and Danish populations (additive model: rs2237895, P = 3.7 x 10(-11); OR = 1.24, rs2237897, P = 1.2 x 10(-4); OR = 1.36).
Unoki
Hiroyuki
H
Laboratory for Endocrinology and Metabolism, Center for Genomic Medicine, RIKEN, Yokohama, Kanagawa 230-0045, Japan.
Takahashi
Atsushi
A
Kawaguchi
Takahisa
T
Hara
Kazuo
K
Horikoshi
Momoko
M
Andersen
Gitte
G
Ng
Daniel P K
DP
Holmkvist
Johan
J
Borch-Johnsen
Knut
K
Jørgensen
Torben
T
Sandbaek
Annelli
A
Lauritzen
Torsten
T
Hansen
Torben
T
Nurbaya
Siti
S
Tsunoda
Tatsuhiko
T
Kubo
Michiaki
M
Babazono
Tetsuya
T
Hirose
Hiroshi
H
Hayashi
Matsuhiko
M
Iwamoto
Yasuhiko
Y
Kashiwagi
Atsunori
A
Kaku
Kohei
K
Kawamori
Ryuzo
R
Tai
E Shyong
ES
Pedersen
Oluf
O
Kamatani
Naoyuki
N
Kadowaki
Takashi
T
Kikkawa
Ryuichi
R
Nakamura
Yusuke
Y
Maeda
Shiro
S
D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D051657:KCNQ1 Potassium Channel / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012846:Singapore; D044465:White People / Q000235:genetics*
D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human