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. 2011 Mar;32(3):548.e9-18.
doi: 10.1016/j.neurobiolaging.2009.11.021. Epub 2009 Dec 24.

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

Rejko Krüger  1 , Manu Sharma, Olaf Riess, Thomas Gasser, Christine Van Broeckhoven, Jessie Theuns, Jan Aasly, Grazia Annesi, Anna Rita Bentivoglio, Alexis Brice, Ana Djarmati, Alexis Elbaz, Matthew Farrer, Carlo Ferrarese, J Mark Gibson, Georgios M Hadjigeorgiou, Nobutaka Hattori, John P A Ioannidis, Barbara Jasinska-Myga, Christine Klein, Jean-Charles Lambert, Suzanne Lesage, Juei-Jueng Lin, Timothy Lynch, George D Mellick, Francesa de Nigris, Grzegorz Opala, Alessandro Prigione, Aldo Quattrone, Owen A Ross, Wataru Satake, Peter A Silburn, Eng King Tan, Tatsushi Toda, Hiroyuki Tomiyama, Karin Wirdefeldt, Zbigniew Wszolek, Georgia Xiromerisiou, Demetrius M Maraganore; Genetic Epidemiology of Parkinson's disease consortium
Collaborators, Affiliations

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

Rejko Krüger et al. Neurobiol Aging. 2011 Mar.

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; 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.

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Conflict of interest statement

Disclosure statement: All authors have reported no actual or potential conflict of interest and have certified that all data contained in this manuscript have not been previously published, have not been submitted elsewhere and will not be submitted elsewhere while under the consideration of Neurobiology of Aging. Appropriate approval and procedures were used concerning human subjects. All authors have reviewed the contents of the manuscript being submitted, approve of its content and validate the accuracy of the data. Should a significant conflict of interest be present, the Editors reserve the right to reject the article on that basis. Funding to investigators was provided by the German Federal Ministry for Education and Research (BMBF, NGFNplus; 01GS08134) to T.G.O.R and R.K. and the German Research Council (DFG, KR2119/3-1) to R.K.; “High-Tech Research Center” Project, Grant-in-Aid for Scientific Research (to N.H., 17390256, and to H.T., 21591098) from the Japanese Ministry of Education, Culture, Sports, Science and Technology; Italian Ministry of Health, Ricerca Finalizzata ex. art. 56, grant nr. ART56-OGR-704795 to E.M.V., the Volk-swagen Foundation and the Hermann and Lilly Schilling Foundation to C.K. and a Rapid Response Innovation Award from the Michael J. Fox Foundation to O.A.R. ; The Morris K. Udall Center, NIH/NINDS P50NS40256, and by P01AG17216, R01NS057567, R01AG15866, R01NS042859, R01NS039422, CIHR121849, and PARF to Z.W.; the Special Research Fund of the University of Antwerp, the Fund for Scientific Research Flanders (FWO-V), the Institute for Science and Technology – Flanders (IWT-V), the Interuniversity Attraction Poles program P6/43 of the Belgian Science Policy Office, the Medical Research Foundation Antwerp and Neurosearch Antwerp and a Methusalem Excellence Grant of the Flemish Government, Flanders, Belgium to the Antwerp site.

Figures

Fig. 1
Fig. 1
A panel showing the forest plot for each SNP. The summary effect estimate is indicated by the diamond (A) Forest plot for SNPs rs10779958, (B) rs1183739, (C) rs2231250, (D) rs2241028 and (E) rs72470544.
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