Meta-Analysis of Differentially Expressed Genes in the Substantia Nigra in Parkinson's Disease Supports Phenotype-Specific Transcriptome Changes

• Published in: Frontiers in neuroscience 2020-12, Vol.14, p.596105-596105
• Main Authors: Phung, Duong My, Lee, Jinwoo, Hong, SangKyoon, Kim, Young Eun, Yoon, Jeehee, Kim, Yun Joong
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Ataxia; Basal ganglia; Central nervous system diseases; Datasets; differentially expressed genes; disease-related genes; DNA microarrays; Dopamine; Gene expression; Genomes; Genotype & phenotype; Meta-analysis; Microglia; Mitochondrial DNA; Movement disorders; Mutation; Neurodegeneration; Neurodegenerative diseases; Neuroscience; Ontology; Parkinson's disease; Phenotypes; Substantia nigra
• ISSN: 1662-4548; 1662-453X; 1662-453X
• DOI: 10.3389/fnins.2020.596105

Studies regarding differentially expressed genes (DEGs) in Parkinson's disease (PD) have focused on common upstream regulators or dysregulated pathways or ontologies; however, the relationships between DEGs and disease-related or cell type-enriched genes have not been systematically studied. Meta-analysis of DEGs (meta-DEGs) are expected to overcome the limitations, such as replication failure and small sample size of previous studies. Meta-DEGs were performed to investigate dysregulated genes enriched with neurodegenerative disorder causative or risk genes in a phenotype-specific manner. Six microarray datasets from PD patients and controls, for which substantia nigra sample transcriptome data were available, were downloaded from the NINDS data repository. Meta-DEGs were performed using two methods, combining -values and combing effect size, and common DEGs were used for secondary analyses. Gene sets of cell type-enriched or disease-related genes for PD, Alzheimer's disease (AD), and hereditary progressive ataxia were constructed by curation of public databases and/or published literatures. Our meta-analyses revealed 449 downregulated and 137 upregulated genes. Overrepresentation analyses with cell type-enriched genes were significant in neuron-enriched genes but not in astrocyte- or microglia-enriched genes. Meta-DEGs were significantly enriched in causative genes for hereditary disorders accompanying parkinsonism but not in genes associated with AD or hereditary progressive ataxia. Enrichment of PD-related genes was highly significant in downregulated DEGs but insignificant in upregulated genes. Downregulated meta-DEGs were associated with PD-related genes, but not with other neurodegenerative disorder genes. These results highlight disease phenotype-specific changes in dysregulated genes in PD.