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
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.