Article (Scientific journals)
A large-scale genetic association study to evaluate the contribution of Omi/HtrA2 (PARK13) to Parkinson's disease.
Krüger, Rejko; Sharma, Manu; Riess, Olaf et al.
2011In Neurobiology of Aging, 32 (3), p. 548.e9-18
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Keywords :
Aged; Chi-Square Distribution; Cohort Studies; European Continental Ancestry Group/ethnology; Female; Gene Frequency; Genetic Predisposition to Disease; Genome-Wide Association Study; Genotype; Humans; International Cooperation; Male; Meta-Analysis as Topic; Middle Aged; Mitochondrial Proteins/genetics; Parkinson Disease/epidemiology/ethnology/genetics; Polymorphism, Single Nucleotide/genetics; Serine Endopeptidases/genetics
Abstract :
[en] 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.
Research center :
- Luxembourg Centre for Systems Biomedicine (LCSB): Clinical & Experimental Neuroscience (Krüger Group)
Disciplines :
Genetics & genetic processes
Author, co-author :
Krüger, Rejko ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Sharma, Manu
Riess, Olaf
Gasser, Thomas
Van Broeckhoven, Christine
Theuns, Jessie
Aasly, Jan
Annesi, Grazia
Bentivoglio, Anna Rita
Brice, Alexis
Djarmati, Ana
Elbaz, Alexis
Farrer, Matthew
Ferrarese, Carlo
Gibson, J. Mark
Hadjigeorgiou, Georgios M.
Hattori, Nobutaka
Ioannidis, John P. A.
Jasinska-Myga, Barbara
Klein, Christine
Lambert, Jean-Charles
Lesage, Suzanne
Lin, Juei-Jueng
Lynch, Timothy
Mellick, George D.
de Nigris, Francesa
Opala, Grzegorz
Prigione, Alessandro
Quattrone, Aldo
Ross, Owen A.
Satake, Wataru
Silburn, Peter A.
Tan, Eng King
Toda, Tatsushi
Tomiyama, Hiroyuki
Wirdefeldt, Karin
Wszolek, Zbigniew
Xiromerisiou, Georgia
Maraganore, Demetrius M.
More authors (29 more) Less
Language :
English
Title :
A large-scale genetic association study to evaluate the contribution of Omi/HtrA2 (PARK13) to Parkinson's disease.
Publication date :
2011
Journal title :
Neurobiology of Aging
ISSN :
1558-1497
Publisher :
Elsevier, Netherlands
Volume :
32
Issue :
3
Pages :
548.e9-18
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
Copyright (c) 2009 Elsevier Inc. All rights reserved.
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