ArticleAnnals of neurology2021
Heritability Enrichment Implicates Microglia in Parkinson's Disease Pathogenesis.
Article in Annals of neurology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.
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Who cites it
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 74 citations in OpenAlex.
- Epigenome-wide association study of human frontal cortex identifies differential methylation in Lewy body pathology.Nature communications · 2022Pooled it
- Integration of cell-specific gene expression and chromatin accessibility facilitates localization of neurodegenerative risk in microglia.bioRxiv : the preprint server for biology · 2026Article
- Article
- Cell type-specific contextualisation of the human phenome: towards the systematic treatment of all rare diseases.Genome medicine · 2026Article
- iSCORE-PD: an isogenic stem cell collection to research Parkinson's disease.Nature communications · 2026Article
- Integrating dorsolateral prefrontal cortex multi-omics and GWAS summary data reveals genetic etiology of Parkinson's disease.Research square · 2026Article
- Integrating dorsolateral prefrontal cortex multi-omics and GWAS summary data reveals genetic etiology of Parkinson's disease.medRxiv : the preprint server for health sciences · 2026Article
- Bidirectional mediation between microbiota and immune system in Parkinson disease: A two-sample Mendelian randomization study.Medicine · 2026Article
- GDNF signaling modulation by Akkermansia muciniphila ameliorates constipation-depression comorbidity in Parkinson's disease.NPJ Parkinson's disease · 2025Article
- Regulatory Genomic Circuitry of Brain Age by Integrative Functional Genomic Analyses.Genomics, proteomics & bioinformatics · 2025Article
- The Role and Mechanisms of G protein-coupled receptors in Parkinson's disease.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025Review
- MHCII reduction is insufficient to protect mice from alpha-synuclein-induced degeneration and the Parkinson's HLA locus exhibits epigenetic regulation.Scientific reports · 2025Article
- Role of Thrombosis in Neurodegenerative Diseases: An Intricate Mechanism of Neurovascular Complications.Molecular neurobiology · 2025Review
- Genetic risk for neurodegenerative conditions is linked to disease-specific microglial pathways.PLoS genetics · 2025Article
- (Dys)regulation of the Immune System in Parkinson's Disease: Methodologies, Techniques, and Key Findings from Human Studies.Aging and disease · 2025Review
- Long-read RNA sequencing atlas of human microglia isoforms elucidates disease-associated genetic regulation of splicing.Nature genetics · 2025Article
- Immune mechanisms and shared immune targets in neurodegenerative diseases.Nature reviews. Neurology · 2025Review
- Novel floxed cannabinoid receptor 2 mouse line combines knockout capability with dual fluorescent reporters.Frontiers in pharmacology · 2025Article
- Article
- An integrated toolkit for human microglia functional genomics.Stem cell research & therapy · 2024Article
Corrections and comments
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Authors and funding
10 authors at 6 institutions in 7 countries.
Funding
Abstract
objectiveUnderstanding how different parts of the immune system contribute to pathogenesis in Parkinson's disease is a burning challenge with important therapeutic implications. We studied enrichment of common variant heritability for Parkinson's disease stratified by immune and brain cell types.
methodsWe used summary statistics from the most recent meta-analysis of genomewide association studies in Parkinson's disease and partitioned heritability using linkage disequilibrium score regression, stratified for specific cell types, as defined by open chromatin regions. We also validated enrichment results using a polygenic risk score approach and intersected disease-associated variants with epigenetic data and expression quantitative loci to nominate and explore a putative microglial locus.
resultsWe found significant enrichment of Parkinson's disease risk heritability in open chromatin regions of microglia and monocytes. Genomic annotations overlapped substantially between these 2 cell types, and only the enrichment signal for microglia remained significant in a joint model. We present evidence suggesting P2RY12, a key microglial gene and target for the antithrombotic agent clopidogrel, as the likely driver of a significant Parkinson's disease association signal on chromosome 3.
interpretationOur results provide further support for the importance of immune mechanisms in Parkinson's disease pathogenesis, highlight microglial dysregulation as a contributing etiological factor, and nominate a targetable microglial gene candidate as a pathogenic player. Immune processes can be modulated by therapy, with potentially important clinical implications for future treatment in Parkinson's disease. ANN NEUROL 2021;89:942-951.
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