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Convergence of miRNA expression profiling, α-synuclein interacton and GWAS in Parkinson's disease

2011Journal article Open access
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dc.contributor.authorMartins, Madalena
dc.contributor.authorRosa, Alexandra
dc.contributor.authorGuedes, Leonor C.
dc.contributor.authorFonseca, Benedita V.
dc.contributor.authorGotovac, Kristina
dc.contributor.authorViolante, Sara
dc.contributor.authorMestre, Tiago
dc.contributor.authorCoelho, Miguel
dc.contributor.authorRosa, Mário M.
dc.contributor.authorMartin, Eden R.
dc.contributor.authorVance, Jeffery M.
dc.contributor.authorOuteiro, Tiago F.
dc.contributor.authorWang, Liyong
dc.contributor.authorBorovecki, Fran
dc.contributor.authorFerreira, Joaquim J.
dc.contributor.authorOliveira, Sofia A.
dc.date.accessioned2022-03-07T15:18:35Z
dc.date.available2022-03-07T15:18:35Z
dc.date.issued2011
dc.description.abstractmiRNAs were recently implicated in the pathogenesis of numerous diseases, including neurological disorders such as Parkinson’s disease (PD). miRNAs are abundant in the nervous system, essential for efficient brain function and play important roles in neuronal patterning and cell specification. To further investigate their involvement in the etiology of PD, we conducted miRNA expression profiling in peripheral blood mononuclear cells (PBMCs) of 19 patients and 13 controls using microarrays. We found 18 miRNAs differentially expressed, and pathway analysis of 662 predicted target genes of 11 of these miRNAs revealed an over-representation in pathways previously linked to PD as well as novel pathways. To narrow down the genes for further investigations, we undertook a parallel approach using chromatin immunoprecipitation-sequencing (ChIP-seq) analysis to uncover genome-wide interactions of a-synuclein, a molecule with a central role in both monogenic and idiopathic PD. Convergence of ChIP-seq and miRNomics data highlighted the glycosphingolipid biosynthesis and the ubiquitin proteasome system as key players in PD. We then tested the association of target genes belonging to these pathways with PD risk, and identified nine SNPs in USP37 consistently associated with PD susceptibility in three genome-wide association studies (GWAS) datasets (0.46#OR#0.63) and highly significant in the meta-dataset (3.3661024 ,p,1.9461023 ). A SNP in ST8SIA4 was also highly associated with PD (p = 6.1561023 ) in the meta-dataset. These findings suggest that several miRNAs may act as regulators of both known and novel biological processes leading to idiopathic PD.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationMartins, M., Rosa, A., Guedes, L. C., Fonseca, B. V., Gotovac, K., Violante, S., ... & Oliveira, S. A. (2011). Convergence of miRNA expression profiling, α-synuclein interacton and GWAS in Parkinson's disease. PloS one, 6(10), e25443. doi:10.1371/journal.pone.0025443pt_PT
dc.identifier.doi10.1371/journal.pone.0025443pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.13/4120
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherPublic Library of Sciencept_PT
dc.relationIDENTIFICATION OF GENETIC RISK FACTORS FOR PARKINSONSDISEASE USING MICRORNOMICS AND PROTEOMICS
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectmiRNA expression profilingpt_PT
dc.subjecta-Synuclein interactonpt_PT
dc.subjectParkinson’s diseasept_PT
dc.subjectGWAS in Parkinson’s diseasept_PT
dc.subject.pt_PT
dc.subjectFaculdade de Ciências da Vidapt_PT
dc.titleConvergence of miRNA expression profiling, α-synuclein interacton and GWAS in Parkinson's diseasept_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleIDENTIFICATION OF GENETIC RISK FACTORS FOR PARKINSONSDISEASE USING MICRORNOMICS AND PROTEOMICS
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FSAU-GMG%2F64428%2F2006/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBPD%2F29354%2F2006/PT
oaire.citation.issue10pt_PT
oaire.citation.startPagee25443pt_PT
oaire.citation.titlePLoS ONEpt_PT
oaire.citation.volume6pt_PT
oaire.fundingStream3599-PPCDT
person.familyNameda Silva Rosa
person.givenNamePatrícia Alexandra
person.identifier.ciencia-idF01B-3B5B-2269
person.identifier.orcid0000-0002-1827-6828
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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relation.isAuthorOfPublication.latestForDiscoverycc0e7b32-45ac-4aad-9256-32bc9de21975
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