TY - JOUR
T1 - A large-scale genetic association study to evaluate the contribution of Omi/HtrA2 (PARK13) to Parkinson's disease
AU - Krüger, Rejko
AU - Sharma, Manu
AU - Riess, Olaf
AU - Gasser, Thomas
AU - Van Broeckhoven, Christine
AU - Theuns, Jessie
AU - Aasly, Jan
AU - Annesi, Grazia
AU - Bentivoglio, Anna Rita
AU - Brice, Alexis
AU - Djarmati, Ana
AU - Elbaz, Alexis
AU - Farrer, Matthew
AU - Ferrarese, Carlo
AU - Gibson, J. Mark
AU - Hadjigeorgiou, Georgios M.
AU - Hattori, Nobutaka
AU - Ioannidis, John P.A.
AU - Jasinska-Myga, Barbara
AU - Klein, Christine
AU - Lambert, Jean Charles
AU - Lesage, Suzanne
AU - Lin, Juei Jueng
AU - Lynch, Timothy
AU - Mellick, George D.
AU - de Nigris, Francesa
AU - Opala, Grzegorz
AU - Prigione, Alessandro
AU - Quattrone, Aldo
AU - Ross, Owen A.
AU - Satake, Wataru
AU - Silburn, Peter A.
AU - Tan, Eng King
AU - Toda, Tatsushi
AU - Tomiyama, Hiroyuki
AU - Wirdefeldt, Karin
AU - Wszolek, Zbigniew
AU - Xiromerisiou, Georgia
AU - Maraganore, Demetrius M.
N1 - Funding Information:
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 Volkswagen 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.
PY - 2011/3
Y1 - 2011/3
N2 - 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.
AB - 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.
KW - Genetics
KW - HtrA2
KW - Omi
KW - PARK13
KW - Parkinson's disease
UR - http://www.scopus.com/inward/record.url?scp=79952900158&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79952900158&partnerID=8YFLogxK
U2 - 10.1016/j.neurobiolaging.2009.11.021
DO - 10.1016/j.neurobiolaging.2009.11.021
M3 - Article
C2 - 20036034
AN - SCOPUS:79952900158
SN - 0197-4580
VL - 32
SP - 548.e9-548.e18
JO - Neurobiology of aging
JF - Neurobiology of aging
IS - 3
ER -