Duong My Phung1, Jinwoo Lee2, SangKyoon Hong3, Young Eun Kim4, Jeehee Yoon2, Yun Joong Kim5,6. 1. Department of Biomedical Gerontology, Ilsong Institute of Life and Science, Hallym University, Anyang, South Korea. 2. Department of Computer Engineering, Hallym University, Chuncheon, South Korea. 3. Hallym Institute of Translational Genomics and Bioinformatics, Anyang, South Korea. 4. Laboratory of Parkinson's Disease and Neurogenetics, Department of Neurology, Hallym University, Anyang, South Korea. 5. Department of Neurology, Yonsei University College of Medicine, Yongin, South Korea. 6. Department of Neurology, Yongin Severance Hospital, Yonsei University Health System, Yongin, South Korea.
Abstract
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.
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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