Genome-wide association study identifies common variants at four loci as genetic risk factors for Parkinson's disease.
To identify susceptibility variants for Parkinson's disease (PD), we performed a genome-wide association study (GWAS) and two replication studies in a total of 2,011 cases and 18,381 controls from Japan. We identified a new susceptibility locus on 1q32 (P = 1.52 x 10(-12)) and designated this as PARK16, and we also identified BST1 on 4p15 as a second new risk locus (P = 3.94 x 10(-9)). We also detected strong associations at SNCA on 4q22 (P = 7.35 x 10(-17)) and LRRK2 on 12q12 (P = 2.72 x 10(-8)), both of which are implicated in autosomal dominant forms of parkinsonism. By comparing results of a GWAS performed on individuals of European ancestry, we identified PARK16, SNCA and LRRK2 as shared risk loci for PD and BST1 and MAPT as loci showing population differences. Our results identify two new PD susceptibility loci, show involvement of autosomal dominant parkinsonism loci in typical PD and suggest that population differences contribute to genetic heterogeneity in PD.
Satake
Wataru
W
Division of Neurology/Molecular Brain Science, Kobe University Graduate School of Medicine, Kobe, Japan.
Nakabayashi
Yuko
Y
Mizuta
Ikuko
I
Hirota
Yushi
Y
Ito
Chiyomi
C
Kubo
Michiaki
M
Kawaguchi
Takahisa
T
Tsunoda
Tatsuhiko
T
Watanabe
Masahiko
M
Takeda
Atsushi
A
Tomiyama
Hiroyuki
H
Nakashima
Kenji
K
Hasegawa
Kazuko
K
Obata
Fumiya
F
Yoshikawa
Takeo
T
Kawakami
Hideshi
H
Sakoda
Saburo
S
Yamamoto
Mitsutoshi
M
Hattori
Nobutaka
N
Murata
Miho
M
Nakamura
Yusuke
Y
Toda
Tatsushi
T
D016022:Case-Control Studies; D005787:Gene Frequency; D018740:Genetic Heterogeneity; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D007564:Japan; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D010300:Parkinson Disease / Q000453:epidemiology / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D012307:Risk Factors; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism
C497604:SNCA protein, human; D051844:alpha-Synuclein; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases