Dissection of the genetics of Parkinson's disease identifies an additional association 5' of SNCA and multiple associated haplotypes at 17q21.
We performed a genome-wide association study (GWAS) in 1705 Parkinson's disease (PD) UK patients and 5175 UK controls, the largest sample size so far for a PD GWAS. Replication was attempted in an additional cohort of 1039 French PD cases and 1984 controls for the 27 regions showing the strongest evidence of association (P< 10(-4)). We replicated published associations in the 4q22/SNCA and 17q21/MAPT chromosome regions (P< 10(-10)) and found evidence for an additional independent association in 4q22/SNCA. A detailed analysis of the haplotype structure at 17q21 showed that there are three separate risk groups within this region. We found weak but consistent evidence of association for common variants located in three previously published associated regions (4p15/BST1, 4p16/GAK and 1q32/PARK16). We found no support for the previously reported SNP association in 12q12/LRRK2. We also found an association of the two SNPs in 4q22/SNCA with the age of onset of the disease.
Wellcome Trust Centre for Human Genetics, Oxford, UK.
Chris C A
CC
Spencer
Vincent
V
Plagnol
Amy
A
Strange
Michelle
M
Gardner
Coro
C
Paisan-Ruiz
Gavin
G
Band
Roger A
RA
Barker
Celine
C
Bellenguez
Kailash
K
Bhatia
Hannah
H
Blackburn
Jennie M
JM
Blackwell
Elvira
E
Bramon
Martin A
MA
Brown
Matthew A
MA
Brown
David
D
Burn
Juan-Pablo
JP
Casas
Patrick F
PF
Chinnery
Carl E
CE
Clarke
Aiden
A
Corvin
Nicholas
N
Craddock
Panos
P
Deloukas
Sarah
S
Edkins
Jonathan
J
Evans
Colin
C
Freeman
Emma
E
Gray
John
J
Hardy
Gavin
G
Hudson
Sarah
S
Hunt
Janusz
J
Jankowski
Cordelia
C
Langford
Andrew J
AJ
Lees
Hugh S
HS
Markus
Christopher G
CG
Mathew
Mark I
MI
McCarthy
Karen E
KE
Morrison
Colin N A
CN
Palmer
Justin P
JP
Pearson
Leena
L
Peltonen
Matti
M
Pirinen
Robert
R
Plomin
Simon
S
Potter
Anna
A
Rautanen
Stephen J
SJ
Sawcer
Zhan
Z
Su
Richard C
RC
Trembath
Ananth C
AC
Viswanathan
Nigel W
NW
Williams
Huw R
HR
Morris
Peter
P
Donnelly
Nicholas W
NW
Wood
D017668:Age of Onset; D016022:Case-Control Studies; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006239:Haplotypes; D006801:Humans; D010300:Parkinson Disease / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D018401:Sample Size; D044465:White People; D051844:alpha-Synuclein / Q000235:genetics*
C497604:SNCA protein, human; D051844:alpha-Synuclein