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

Authors
 Duong My Phung  ;  Jinwoo Lee  ;  SangKyoon Hong  ;  Young Eun Kim  ;  Jeehee Yoon  ;  Yun Joong Kim 
Citation
 FRONTIERS IN NEUROSCIENCE, Vol.14 : 596105, 2020-12 
Journal Title
 FRONTIERS IN NEUROSCIENCE 
ISSN
 1662-4548 
Issue Date
2020-12
Keywords
Parkinson’s disease ; differentially expressed genes ; disease-related genes ; meta-analysis ; substantia nigra
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.
Files in This Item:
T202005719.pdf Download
DOI
10.3389/fnins.2020.596105
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Neurology (신경과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Yun Joong(김윤중) ORCID logo https://orcid.org/0000-0002-2956-1552
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/181439
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