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dc.creatorStorm, Catherine S.es
dc.creatorKia, Demis A.es
dc.creatorAlmramhi, Mona M.es
dc.creatorBandres-Ciga, Saraes
dc.creatorFinan, Chrises
dc.creatorHingorani, Aroon D.es
dc.creatorWood, Nicholas W.es
dc.creatorMir Rivera, Pabloes
dc.creatorPeriñán Tocino, María Teresaes
dc.date.accessioned2022-11-29T17:36:51Z
dc.date.available2022-11-29T17:36:51Z
dc.date.issued2021-12-20
dc.identifier.citationStorm, C.S., Kia, D.A., Almramhi, M.M., Bandres-Ciga, S., Finan, C., Hingorani, A.D.,...,Periñán Tocino, M.T. (2021). Finding genetically-supported drug targets for Parkinson’s disease using Mendelian randomization of the druggable genome. Nature Communications, 12 (1), 7342. https://doi.org/10.1038/s41467-021-26280-1.
dc.identifier.issn2041-1723es
dc.identifier.urihttps://hdl.handle.net/11441/139902
dc.description.abstractParkinson’s disease is a neurodegenerative movement disorder that currently has no disease-modifying treatment, partly owing to inefficiencies in drug target identification and validation. We use Mendelian randomization to investigate over 3,000 genes that encode druggable proteins and predict their efficacy as drug targets for Parkinson’s disease. We use expression and protein quantitative trait loci to mimic exposure to medications, and we examine the causal effect on Parkinson’s disease risk (in two large cohorts), age at onset and progression. We propose 23 drug-targeting mechanisms for Parkinson’s disease, including four possible drug repurposing opportunities and two drugs which may increase Parkinson’s disease risk. Of these, we put forward six drug targets with the strongest Mendelian randomization evidence. There is remarkably little overlap between our drug targets to reduce Parkinson’s disease risk versus progression, suggesting different molecular mechanisms. Drugs with genetic support are considerably more likely to succeed in clinical trials, and we provide compelling genetic evidence and an analysis pipeline to prioritise Parkinson’s disease drug development.es
dc.formatapplication/pdfes
dc.format.extent14 p.es
dc.language.isoenges
dc.publisherNature Researches
dc.relation.ispartofNature Communications, 12 (1), 7342.
dc.rightsAtribución 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.titleFinding genetically-supported drug targets for Parkinson’s disease using Mendelian randomization of the druggable genomees
dc.typeinfo:eu-repo/semantics/articlees
dcterms.identifierhttps://ror.org/03yxnpp24
dc.type.versioninfo:eu-repo/semantics/publishedVersiones
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses
dc.contributor.affiliationUniversidad de Sevilla. Departamento de Medicinaes
dc.relation.publisherversionhttps://www.nature.com/articles/s41467-021-26280-1es
dc.identifier.doi10.1038/s41467-021-26280-1es
dc.journaltitleNature Communicationses
dc.publication.volumen12es
dc.publication.issue1es
dc.publication.initialPage7342es

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