A large-scale genetic association study to evaluate the contribution of Omi/HtrA2 (PARK13) to Parkinson's disease

Kruger, Rejko, 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, Z., Xiromerisiou, Georgia and Maraganore, Demetrius M. (2011) A large-scale genetic association study to evaluate the contribution of Omi/HtrA2 (PARK13) to Parkinson's disease. Neurobiology of Aging, 32 3: 548.e9-548.e18. doi:10.1016/j.neurobiolaging.2009.11.021


Author Kruger, Rejko
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, Z.
Xiromerisiou, Georgia
Maraganore, Demetrius M.
Title A large-scale genetic association study to evaluate the contribution of Omi/HtrA2 (PARK13) to Parkinson's disease
Journal name Neurobiology of Aging   Check publisher's open access policy
ISSN 0197-4580
1558-1497
Publication date 2011-03
Year available 2010
Sub-type Article (original research)
DOI 10.1016/j.neurobiolaging.2009.11.021
Volume 32
Issue 3
Start page 548.e9
End page 548.e18
Total pages 10
Place of publication Elmsford, NY, U.S.A.
Publisher Pergamon
Collection year 2011
Language eng
Formatted abstract
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; I2 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. © 2009 Elsevier Inc.
Keyword Genetics
HtrA2
Omi
PARK13
Parkinson's disease
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online 23 December, 2010. For the Genetic Epidemiology of Parkinson’s disease consortium

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
Official 2011 Collection
 
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Created: Fri, 18 Feb 2011, 15:06:28 EST by Caroline Irle on behalf of UQ Centre for Clinical Research