ArticleHuman molecular genetics2023
Integration of transcriptome-wide association study with neuronal dysfunction assays provides functional genomics evidence for Parkinson's disease genes.
Article in Human molecular genetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Novel Insights Into the Causal Effects and Shared Genetics Between Body Fat and Parkinson Disease.CNS neuroscience & therapeutics · 2024Pooled it
- Molecular Mechanisms of Neurodegenerative Diseases: Emerging Biomarkers and Therapeutic Targets.Brain sciences · 2026Review
- Systems genetic dissection of brain gene expression reveals excitotoxic mechanisms of Alzheimer's disease.Molecular psychiatry · 2026Article
- DNA Methylation Regulates CDK5R1 and NRBP1 to Exert Effects on Alcohol Dependence: Insights From Mendelian Randomization.Addiction biology · 2026Article
- Neural networks reveal novel gene signatures in Parkinson disease from single-nuclei transcriptomes.NPJ Parkinson's disease · 2025Article
- The integration of genome-wide and transcriptome-wide association studies in neurodegenerative diseases: opportunities, challenges, and current methodological innovations.Briefings in bioinformatics · 2025Review
- Unlocking Parkinson's disease: the role of microRNAs in regulation, diagnosis, and therapy.Apoptosis : an international journal on programmed cell death · 2025Review
- Haploinsufficiency of ITSN1 is associated with a substantial increased risk of Parkinson's disease.Cell reports · 2025Article
- Longitudinal multi-omics in alpha-synuclein Drosophila model discriminates disease- from age-associated pathologies in Parkinson's disease.NPJ Parkinson's disease · 2025Article
- Characterisation of the function of a lncRNA containing SINE-VNTR-Alu 67 to regulate the genes at theExperimental biology and medicine (Maywood, N.J.) · 2025Article
- A multi-omics Mendelian randomization study identifies new therapeutic targets for alcohol use disorder and problem drinking.Nature human behaviour · 2025Article
- Joint-tissue integrative analysis identifies high-risk genes for Parkinson's disease.Frontiers in neuroscience · 2024Article
- A CYPome-wide study reveals new potential players in the pathogenesis of Parkinson's disease.Frontiers in pharmacology · 2022Article
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11 authors.
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Abstract
Genome-wide association studies (GWAS) have markedly advanced our understanding of the genetics of Parkinson's disease (PD), but they currently do not account for the full heritability of PD. In many cases it is difficult to unambiguously identify a specific gene within each locus because GWAS does not provide functional information on the identified candidate loci. Here we present an integrative approach that combines transcriptome-wide association study (TWAS) with high-throughput neuronal dysfunction analyses in Drosophila to discover and validate candidate PD genes. We identified 160 candidate genes whose misexpression is associated with PD risk via TWAS. Candidates were validated using orthogonal in silico methods and found to be functionally related to PD-associated pathways (i.e. endolysosome). We then mimicked these TWAS-predicted transcriptomic alterations in a Drosophila PD model and discovered that 50 candidates can modulate α-Synuclein(α-Syn)-induced neurodegeneration, allowing us to nominate new genes in previously known PD loci. We also uncovered additional novel PD candidate genes within GWAS suggestive loci (e.g. TTC19, ADORA2B, LZTS3, NRBP1, HN1L), which are also supported by clinical and functional evidence. These findings deepen our understanding of PD, and support applying our integrative approach to other complex trait disorders.
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