Genome-wide association study identifies three novel loci for type 2 diabetes.
Although over 60 loci for type 2 diabetes (T2D) have been identified, there still remains a large genetic component to be clarified. To explore unidentified loci for T2D, we performed a genome-wide association study (GWAS) of 6 209 637 single-nucleotide polymorphisms (SNPs), which were directly genotyped or imputed using East Asian references from the 1000 Genomes Project (June 2011 release) in 5976 Japanese patients with T2D and 20 829 nondiabetic individuals. Nineteen unreported loci were selected and taken forward to follow-up analyses. Combined discovery and follow-up analyses (30 392 cases and 34 814 controls) identified three new loci with genome-wide significance, which were MIR129-LEP [rs791595; risk allele = A; risk allele frequency (RAF) = 0.080; P = 2.55 × 10(-13); odds ratio (OR) = 1.17], GPSM1 [rs11787792; risk allele = A; RAF = 0.874; P = 1.74 × 10(-10); OR = 1.15] and SLC16A13 (rs312457; risk allele = G; RAF = 0.078; P = 7.69 × 10(-13); OR = 1.20). This study demonstrates that GWASs based on the imputation of genotypes using modern reference haplotypes such as that from the 1000 Genomes Project data can assist in identification of new loci for common diseases.
Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.
Kazuo
K
Hara
Hayato
H
Fujita
Todd A
TA
Johnson
Toshimasa
T
Yamauchi
Kazuki
K
Yasuda
Momoko
M
Horikoshi
Chen
C
Peng
Cheng
C
Hu
Ronald C W
RC
Ma
Minako
M
Imamura
Minoru
M
Iwata
Tatsuhiko
T
Tsunoda
Takashi
T
Morizono
Nobuhiro
N
Shojima
Wing Yee
WY
So
Ting Fan
TF
Leung
Patrick
P
Kwan
Rong
R
Zhang
Jie
J
Wang
Weihui
W
Yu
Hiroshi
H
Maegawa
Hiroshi
H
Hirose
Kohei
K
Kaku
Chikako
C
Ito
Hirotaka
H
Watada
Yasushi
Y
Tanaka
Kazuyuki
K
Tobe
Atsunori
A
Kashiwagi
Ryuzo
R
Kawamori
Weiping
W
Jia
Juliana C N
JC
Chan
Yik Ying
YY
Teo
Tai E
TE
Shyong
Naoyuki
N
Kamatani
Michiaki
M
Kubo
Shiro
S
Maeda
Takashi
T
Kadowaki
D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D015894:Genome, Human; D055106:Genome-Wide Association Study; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D020738:Leptin / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics; D027501:Monocarboxylic Acid Transporters / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
C525615:GPSM1 protein, human; D020730:Guanine Nucleotide Dissociation Inhibitors; D020738:Leptin; D035683:MicroRNAs; C541915:Mirn129 microRNA, human; D027501:Monocarboxylic Acid Transporters; C000590224:Slc16a13 protein, human