A large-scale genetic association study to evaluate the contribution of Omi/HtrA2 (PARK13) to Parkinson's disease.
High-profile studies have provided conflicting results regarding the involvement of the Omi/HtrA2 gene in Parkinson's disease (PD) susceptibility. Therefore, we performed a large-scale analysis of the association of common Omi/HtrA2 variants in the Genetic Epidemiology of Parkinson's disease (GEO-PD) consortium. GEO-PD sites provided clinical and genetic data including affection status, gender, ethnicity, age at study, age at examination (all subjects); age at onset and family history of PD (patients). Genotyping was performed for the five most informative SNPs spanning the Omi/HtrA2 gene in approximately 2-3 kb intervals (rs10779958, rs2231250, rs72470544, rs1183739, rs2241028). Fixed as well as random effect models were used to provide summary risk estimates of Omi/HtrA2 variants. The 20 GEO-PD sites provided data for 6378 cases and 8880 controls. No overall significant associations for the five Omi/HtrA2 SNPs and PD were observed using either fixed effect or random effect models. The summary odds ratios ranged between 0.98 and 1.08 and the estimates of between-study heterogeneity were not large (non-significant Q statistics for all 5 SNPs; I(2) estimates 0-28%). Trends for association were seen for participants of Scandinavian descent for rs2241028 (OR 1.41, p=0.04) and for rs1183739 for age at examination (cut-off 65 years; OR 1.17, p=0.02), but these would not be significant after adjusting for multiple comparisons and their Bayes factors were only modest. This largest association study performed to define the role of any gene in the pathogenesis of Parkinson's disease revealed no overall strong association of Omi/HtrA2 variants with PD in populations worldwide.
Krüger
Rejko
R
Laboratory of Functional Neurogenomics, Center of Neurology and Hertie-Institute for Clinical Brain Research, University of Tübingen, Germany. rejko.krueger@uni-tuebingen.de
Sharma
Manu
M
Riess
Olaf
O
Gasser
Thomas
T
Van Broeckhoven
Christine
C
Theuns
Jessie
J
Aasly
Jan
J
Annesi
Grazia
G
Bentivoglio
Anna Rita
AR
Brice
Alexis
A
Djarmati
Ana
A
Elbaz
Alexis
A
Farrer
Matthew
M
Ferrarese
Carlo
C
Gibson
J Mark
JM
Hadjigeorgiou
Georgios M
GM
Hattori
Nobutaka
N
Ioannidis
John P A
JP
Jasinska-Myga
Barbara
B
Klein
Christine
C
Lambert
Jean-Charles
JC
Lesage
Suzanne
S
Lin
Juei-Jueng
JJ
Lynch
Timothy
T
Mellick
George D
GD
de Nigris
Francesa
F
Opala
Grzegorz
G
Prigione
Alessandro
A
Quattrone
Aldo
A
Ross
Owen A
OA
Satake
Wataru
W
Silburn
Peter A
PA
Tan
Eng King
EK
Toda
Tatsushi
T
Tomiyama
Hiroyuki
H
Wirdefeldt
Karin
K
Wszolek
Zbigniew
Z
Xiromerisiou
Georgia
G
Maraganore
Demetrius M
DM
D000368:Aged; D016009:Chi-Square Distribution; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D000074923:High-Temperature Requirement A Serine Peptidase 2; D006801:Humans; D007391:International Cooperation; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics*; D010300:Parkinson Disease / Q000453:epidemiology / Q000208:ethnology* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012697:Serine Endopeptidases / Q000235:genetics*; D044465:White People / Q000208:ethnology
D024101:Mitochondrial Proteins; D012697:Serine Endopeptidases; C000615914:HTRA2 protein, human; D000074923:High-Temperature Requirement A Serine Peptidase 2