title: Genome-wide association study reveals genetic risk underlying Parkinson's disease.
abstract: We performed a genome-wide association study (GWAS) in 1,713 individuals of European ancestry with Parkinson's disease (PD) and 3,978 controls. After replication in 3,361 cases and 4,573 controls, we observed two strong association signals, one in the gene encoding alpha-synuclein (SNCA; rs2736990, OR = 1.23, P = 2.24 x 10(-16)) and another at the MAPT locus (rs393152, OR = 0.77, P = 1.95 x 10(-16)). We exchanged data with colleagues performing a GWAS in Japanese PD cases. Association to PD at SNCA was replicated in the Japanese GWAS, confirming this as a major risk locus across populations. We replicated the effect of a new locus detected in the Japanese cohort (PARK16, rs823128, OR = 0.66, P = 7.29 x 10(-8)) and provide supporting evidence that common variation around LRRK2 modulates risk for PD (rs1491923, OR = 1.14, P = 1.55 x 10(-5)). These data demonstrate an unequivocal role for common genetic variants in the etiology of typical PD and suggest population-specific genetic heterogeneity in this disease.
authors.affiliation: Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Javier
authors.initials: J
authors.lastname: Simón-Sánchez
authors.forename: Claudia
authors.initials: C
authors.lastname: Schulte
authors.forename: Jose M
authors.initials: JM
authors.lastname: Bras
authors.forename: Manu
authors.initials: M
authors.lastname: Sharma
authors.forename: J Raphael
authors.initials: JR
authors.lastname: Gibbs
authors.forename: Daniela
authors.initials: D
authors.lastname: Berg
authors.forename: Coro
authors.initials: C
authors.lastname: Paisan-Ruiz
authors.forename: Peter
authors.initials: P
authors.lastname: Lichtner
authors.forename: Sonja W
authors.initials: SW
authors.lastname: Scholz
authors.forename: Dena G
authors.initials: DG
authors.lastname: Hernandez
authors.forename: Rejko
authors.initials: R
authors.lastname: Krüger
authors.forename: Monica
authors.initials: M
authors.lastname: Federoff
authors.forename: Christine
authors.initials: C
authors.lastname: Klein
authors.forename: Alison
authors.initials: A
authors.lastname: Goate
authors.forename: Joel
authors.initials: J
authors.lastname: Perlmutter
authors.forename: Michael
authors.initials: M
authors.lastname: Bonin
authors.forename: Michael A
authors.initials: MA
authors.lastname: Nalls
authors.forename: Thomas
authors.initials: T
authors.lastname: Illig
authors.forename: Christian
authors.initials: C
authors.lastname: Gieger
authors.forename: Henry
authors.initials: H
authors.lastname: Houlden
authors.forename: Michael
authors.initials: M
authors.lastname: Steffens
authors.forename: Michael S
authors.initials: MS
authors.lastname: Okun
authors.forename: Brad A
authors.initials: BA
authors.lastname: Racette
authors.forename: Mark R
authors.initials: MR
authors.lastname: Cookson
authors.forename: Kelly D
authors.initials: KD
authors.lastname: Foote
authors.forename: Hubert H
authors.initials: HH
authors.lastname: Fernandez
authors.forename: Bryan J
authors.initials: BJ
authors.lastname: Traynor
authors.forename: Stefan
authors.initials: S
authors.lastname: Schreiber
authors.forename: Sampath
authors.initials: S
authors.lastname: Arepalli
authors.forename: Ryan
authors.initials: R
authors.lastname: Zonozi
authors.forename: Katrina
authors.initials: K
authors.lastname: Gwinn
authors.forename: Marcel
authors.initials: M
authors.lastname: van der Brug
authors.forename: Grisel
authors.initials: G
authors.lastname: Lopez
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Chanock
authors.forename: Arthur
authors.initials: A
authors.lastname: Schatzkin
authors.forename: Yikyung
authors.initials: Y
authors.lastname: Park
authors.forename: Albert
authors.initials: A
authors.lastname: Hollenbeck
authors.forename: Jianjun
authors.initials: J
authors.lastname: Gao
authors.forename: Xuemei
authors.initials: X
authors.lastname: Huang
authors.forename: Nick W
authors.initials: NW
authors.lastname: Wood
authors.forename: Delia
authors.initials: D
authors.lastname: Lorenz
authors.forename: Günther
authors.initials: G
authors.lastname: Deuschl
authors.forename: Honglei
authors.initials: H
authors.lastname: Chen
authors.forename: Olaf
authors.initials: O
authors.lastname: Riess
authors.forename: John A
authors.initials: JA
authors.lastname: Hardy
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Singleton
authors.forename: Thomas
authors.initials: T
authors.lastname: Gasser
mesh_terms: D015331:Cohort Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D007564:Japan; D010300:Parkinson Disease / Q000453:epidemiology / Q000235:genetics*; D012307:Risk Factors