Moving beyond neurons: the role of cell type-specific gene regulation in Parkinson's disease heritability

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dc.contributor.authorReynolds, R.H.
dc.contributor.authorBotia, J.
dc.contributor.authorNalls, M.A.
dc.contributor.authorInternational Parkinson's Disease Genomics Consortium (IPDGC)
dc.contributor.authorOkubadejo, N.U.
dc.contributor.authorOjo, O.O.
dc.contributor.authorSystems Genomics of Parkinson Disease
dc.contributor.authorHardy, J.
dc.contributor.authorGagliano Taliun, S.A.
dc.contributor.authorRyten, M.
dc.date.accessioned2019-11-12T13:53:54Z
dc.date.available2019-11-12T13:53:54Z
dc.date.issued2019-04-17
dc.descriptionStaff publicationsen_US
dc.description.abstractParkinson's disease (PD), with its characteristic loss of nigrostriatal dopaminergic neurons and deposition of α-synuclein in neurons, is often considered a neuronal disorder. However, in recent years substantial evidence has emerged to implicate glial cell types, such as astrocytes and microglia. In this study, we used stratified LD score regression and expression-weighted cell-type enrichment together with several brain-related and cell-type-specific genomic annotations to connect human genomic PD findings to specific brain cell types. We found that PD heritability attributable to common variation does not enrich in global and regional brain annotations or brain-related cell-type-specific annotations. Likewise, we found no enrichment of PD susceptibility genes in brain-related cell types. In contrast, we demonstrated a significant enrichment of PD heritability in a curated lysosomal gene set highly expressed in astrocytic, microglial, and oligodendrocyte subtypes, and in LoF-intolerant genes, which were found highly expressed in almost all tested cellular subtypes. Our results suggest that PD risk loci do not lie in specific cell types or individual brain regions, but rather in global cellular processes detectable across several cell types.en_US
dc.identifier.citationReynolds RH, Botía J, Nalls MA; International Parkinson’s Disease Genomics Consortium (IPDGC); System Genomics of Parkinson’s Disease (SGPD), Hardy J, Gagliano Taliun SA, Ryten M. Moving beyond neurons: the role of cell type-specific gene regulation in Parkinson's disease heritability. NPJ Parkinsons Dis. 2019 Apr 17;5:6.en_US
dc.identifier.otherdoi: 10.1038/s41531-019-0076-6.
dc.identifier.urihttps://ir.unilag.edu.ng/handle/123456789/6835
dc.language.isoenen_US
dc.publisherNature Publishing Groupen_US
dc.subjectParkinson diseaseen_US
dc.subjectGeneticsen_US
dc.subjectNeuroscienceen_US
dc.subjectResearch Subject Categories::MEDICINEen_US
dc.titleMoving beyond neurons: the role of cell type-specific gene regulation in Parkinson's disease heritabilityen_US
dc.typeArticleen_US
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