Genome-wide association study reveals genetic risk underlying Parkinson's disease.
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.
Simón-Sánchez
Javier
J
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA.
Schulte
Claudia
C
Bras
Jose M
JM
Sharma
Manu
M
Gibbs
J Raphael
JR
Berg
Daniela
D
Paisan-Ruiz
Coro
C
Lichtner
Peter
P
Scholz
Sonja W
SW
Hernandez
Dena G
DG
Krüger
Rejko
R
Federoff
Monica
M
Klein
Christine
C
Goate
Alison
A
Perlmutter
Joel
J
Bonin
Michael
M
Nalls
Michael A
MA
Illig
Thomas
T
Gieger
Christian
C
Houlden
Henry
H
Steffens
Michael
M
Okun
Michael S
MS
Racette
Brad A
BA
Cookson
Mark R
MR
Foote
Kelly D
KD
Fernandez
Hubert H
HH
Traynor
Bryan J
BJ
Schreiber
Stefan
S
Arepalli
Sampath
S
Zonozi
Ryan
R
Gwinn
Katrina
K
van der Brug
Marcel
M
Lopez
Grisel
G
Chanock
Stephen J
SJ
Schatzkin
Arthur
A
Park
Yikyung
Y
Hollenbeck
Albert
A
Gao
Jianjun
J
Huang
Xuemei
X
Wood
Nick W
NW
Lorenz
Delia
D
Deuschl
Günther
G
Chen
Honglei
H
Riess
Olaf
O
Hardy
John A
JA
Singleton
Andrew B
AB
Gasser
Thomas
T
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