title: Genome-wide association study identifies common variants at four loci as genetic risk factors for Parkinson's disease.
abstract: 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.
authors.affiliation: Division of Neurology/Molecular Brain Science, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Satake
authors.forename: Yuko
authors.initials: Y
authors.lastname: Nakabayashi
authors.forename: Ikuko
authors.initials: I
authors.lastname: Mizuta
authors.forename: Yushi
authors.initials: Y
authors.lastname: Hirota
authors.forename: Chiyomi
authors.initials: C
authors.lastname: Ito
authors.forename: Michiaki
authors.initials: M
authors.lastname: Kubo
authors.forename: Takahisa
authors.initials: T
authors.lastname: Kawaguchi
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Tsunoda
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takeda
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tomiyama
authors.forename: Kenji
authors.initials: K
authors.lastname: Nakashima
authors.forename: Kazuko
authors.initials: K
authors.lastname: Hasegawa
authors.forename: Fumiya
authors.initials: F
authors.lastname: Obata
authors.forename: Takeo
authors.initials: T
authors.lastname: Yoshikawa
authors.forename: Hideshi
authors.initials: H
authors.lastname: Kawakami
authors.forename: Saburo
authors.initials: S
authors.lastname: Sakoda
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Hattori
authors.forename: Miho
authors.initials: M
authors.lastname: Murata
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Tatsushi
authors.initials: T
authors.lastname: Toda
mesh_terms: 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
chemical_list: 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