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

dc.creatorKrüger, R.en
dc.creatorSharma, M.en
dc.creatorRiess, O.en
dc.creatorGasser, T.en
dc.creatorVan Broeckhoven, C.en
dc.creatorTheuns, J.en
dc.creatorAasly, J.en
dc.creatorAnnesi, G.en
dc.creatorBentivoglio, A. R.en
dc.creatorBrice, A.en
dc.creatorDjarmati, A.en
dc.creatorElbaz, A.en
dc.creatorFarrer, M.en
dc.creatorFerrarese, C.en
dc.creatorGibson, J. M.en
dc.creatorHadjigeorgiou, G. M.en
dc.creatorHattori, N.en
dc.creatorIoannidis, J. P. A.en
dc.creatorJasinska-Myga, B.en
dc.creatorKlein, C.en
dc.creatorLambert, J. C.en
dc.creatorLesage, S.en
dc.creatorLin, J. J.en
dc.creatorLynch, T.en
dc.creatorMellick, G. D.en
dc.creatorde Nigris, F.en
dc.creatorOpala, G.en
dc.creatorPrigione, A.en
dc.creatorQuattrone, A.en
dc.creatorRoss, O. A.en
dc.creatorSatake, W.en
dc.creatorSilburn, P. A.en
dc.creatorTan, E. K.en
dc.creatorToda, T.en
dc.creatorTomiyama, H.en
dc.creatorWirdefeldt, K.en
dc.creatorWszolek, Z.en
dc.creatorXiromerisiou, G.en
dc.creatorMaraganore, D. M.en
dc.date.accessioned2015-11-23T10:37:07Z
dc.date.available2015-11-23T10:37:07Z
dc.date.issued2011
dc.identifier10.1016/j.neurobiolaging.2009.11.021
dc.identifier.issn1974580
dc.identifier.urihttp://hdl.handle.net/11615/30055
dc.description.abstractHigh-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.en
dc.sourceNeurobiology of Agingen
dc.source.urihttp://www.scopus.com/inward/record.url?eid=2-s2.0-79952900158&partnerID=40&md5=61623eef1476e5e0737058f20d4e29f0
dc.subjectGeneticsen
dc.subjectHtrA2en
dc.subjectOmien
dc.subjectPARK13en
dc.subjectParkinson's diseaseen
dc.subjectserine proteinase Omien
dc.subjectadulten
dc.subjectageen
dc.subjectarticleen
dc.subjectBayes theoremen
dc.subjectcontrolled studyen
dc.subjectdisease predispositionen
dc.subjectethnicityen
dc.subjectfamily historyen
dc.subjectfemaleen
dc.subjectgenderen
dc.subjectgeneen
dc.subjectgenetic associationen
dc.subjectgenotypeen
dc.subjecthumanen
dc.subjectmajor clinical studyen
dc.subjectmaleen
dc.subjectOmi/Htra2 geneen
dc.subjectonset ageen
dc.subjectParkinson diseaseen
dc.subjectpathogenesisen
dc.subjectpriority journalen
dc.subjectprotein varianten
dc.subjectrisk assessmenten
dc.subjectScandinaviaen
dc.subjectAgeden
dc.subjectChi-Square Distributionen
dc.subjectCohort Studiesen
dc.subjectEuropean Continental Ancestry Groupen
dc.subjectGene Frequencyen
dc.subjectGenetic Predisposition to Diseaseen
dc.subjectGenome-Wide Association Studyen
dc.subjectHumansen
dc.subjectInternational Cooperationen
dc.subjectMeta-Analysis as Topicen
dc.subjectMiddle Ageden
dc.subjectMitochondrial Proteinsen
dc.subjectPolymorphism, Single Nucleotideen
dc.subjectSerine Endopeptidasesen
dc.titleA large-scale genetic association study to evaluate the contribution of Omi/HtrA2 (PARK13) to Parkinson's diseaseen
dc.typejournalArticleen


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