A genome-wide association study in the Japanese population identifies susceptibility loci for type 2 diabetes at UBE2E2 and C2CD4A-C2CD4B.
We conducted a genome-wide association study of type 2 diabetes (T2D) using 459,359 SNPs in a Japanese population with a three-stage study design (stage 1, 4,470 cases and 3,071 controls; stage 2, 2,886 cases and 3,087 controls; stage 3, 3,622 cases and 2,356 controls). We identified new associations in UBE2E2 on chromosome 3 and in C2CD4A-C2CD4B on chromosome 15 at genome-wide significant levels (rs7612463 in UBE2E2, combined P = 2.27 × 10⁻⁹; rs7172432 in C2CD4A-C2CD4B, combined P = 3.66 × 10⁻⁹). The association of these two loci with T2D was replicated in other east Asian populations. In the European populations, the C2CD4A-C2CD4B locus was significantly associated with T2D, and a combined analysis of all populations gave P = 8.78 × 10⁻¹⁴, whereas the UBE2E2 locus did not show association to T2D. In conclusion, we identified two new loci at UBE2E2 and C2CD4A-C2CD4B associated with susceptibility to T2D.
Yamauchi
Toshimasa
T
Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. kadowaki-3im@h.u-tokyo.ac.jp
Hara
Kazuo
K
Maeda
Shiro
S
Yasuda
Kazuki
K
Takahashi
Atsushi
A
Horikoshi
Momoko
M
Nakamura
Masahiro
M
Fujita
Hayato
H
Grarup
Niels
N
Cauchi
Stephane
S
Ng
Daniel P K
DP
Ma
Ronald C W
RC
Tsunoda
Tatsuhiko
T
Kubo
Michiaki
M
Watada
Hirotaka
H
Maegawa
Hiroshi
H
Okada-Iwabu
Miki
M
Iwabu
Masato
M
Shojima
Nobuhiro
N
Shin
Hyoung Doo
HD
Andersen
Gitte
G
Witte
Daniel R
DR
Jørgensen
Torben
T
Lauritzen
Torsten
T
Sandbæk
Annelli
A
Hansen
Torben
T
Ohshige
Toshihiko
T
Omori
Shintaro
S
Saito
Ikuo
I
Kaku
Kohei
K
Hirose
Hiroshi
H
So
Wing-Yee
WY
Beury
Delphine
D
Chan
Juliana C N
JC
Park
Kyong Soo
KS
Tai
E Shyong
ES
Ito
Chikako
C
Tanaka
Yasushi
Y
Kashiwagi
Atsunori
A
Kawamori
Ryuzo
R
Kasuga
Masato
M
Froguel
Philippe
P
Pedersen
Oluf
O
Kamatani
Naoyuki
N
Nakamura
Yusuke
Y
Kadowaki
Takashi
T
D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D009687:Nuclear Proteins; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics*
C494527:C2CD4A protein, human; C494528:C2CD4B protein, human; D009687:Nuclear Proteins; D014157:Transcription Factors; C106347:UBE2E2 protein, human; D044763:Ubiquitin-Conjugating Enzymes
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