Table_2_Meta-Analysis of Differentially Expressed Genes in the Substantia Nigra in Parkinson’s Disease Supports Phenotype-Specific Transcriptome Chang.XLSX (50.74 kB)
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Table_2_Meta-Analysis of Differentially Expressed Genes in the Substantia Nigra in Parkinson’s Disease Supports Phenotype-Specific Transcriptome Changes.XLSX

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posted on 18.12.2020, 04:25 authored by Duong My Phung, Jinwoo Lee, SangKyoon Hong, Young Eun Kim, Jeehee Yoon, Yun Joong Kim
Background

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.

Purpose

Meta-DEGs were performed to investigate dysregulated genes enriched with neurodegenerative disorder causative or risk genes in a phenotype-specific manner.

Methods

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 p-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.

Results

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.

Conclusion

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.

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