Analysis of GWAS-linked loci in Parkinson disease reaffirms PARK16 as a susceptibility locus.
OBJECTIVE
A genome-wide association study (GWAS) in the Japanese population identified 2 new Parkinson disease (PD) susceptibility loci on 1q32 (PARK16) (OMIM 613164) and BST1. We analyzed single nucleotide polymorphism (SNPs) located at the GWAS-linked loci (PARK16, PARK8, PARK1, and BST1) in a Chinese population and also conducted a meta-analysis in Asians by pooling 2 independent replication studies from Japan.


METHODS
We conducted an analysis of 13 SNPs associated with PD GWAS-linked loci in 2 case-control cohorts comprised of 1,349 ethnic Chinese subjects.


RESULTS
PARK16, PARK8, and PARK1 loci but not BST1 were found to be associated with PD. PARK16 SNPs were associated with a decreased risk while PARK1 and PARK8 SNPs were associated with an increased risk of PD. A pooled analysis of our Chinese cohorts and 2 Japanese replication cohorts involving 1,366 subjects with PD and 16,669 controls revealed robust association with these 3 loci and also BST1. There was a trend toward a stronger protective effect of SNPs at the PARK16 locus in sporadic PD compared to familial cases and in older compared to younger subjects.


CONCLUSIONS
Our study reaffirms the role of GWAS-linked loci in PD in Asian subjects and the strength of association is similar between Chinese and Japanese subjects. Efforts to elucidate the associated gene within PARK16 locus are warranted.
Tan
E-K
EK
Department of Neurology, Singapore General Hospital, Singapore. gnrtek@sgh.com.sg
Kwok
H-H
HH
Kwok
H-K
HK
Tan
L C
LC
Zhao
W-T
WT
Prakash
K M
KM
Au
W-L
WL
Pavanni
R
R
Ng
Y-Y
YY
Satake
W
W
Zhao
Y
Y
Toda
T
T
Liu
J-J
JJ
D036541:ADP-ribosyl Cyclase / Q000235:genetics; D015703:Antigens, CD / Q000235:genetics; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D058851:GPI-Linked Proteins; D056426:Genetic Loci / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods*; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000175:diagnosis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D051844:alpha-Synuclein / Q000235:genetics
D015703:Antigens, CD; D058851:GPI-Linked Proteins; 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; D036541:ADP-ribosyl Cyclase; C087521:ADP-ribosyl cyclase 2