Identification of Parkinson’s disease-related pathways and potential risk factors

Abstract

Objective To identify Parkinson’s disease (PD)-associated deregulated pathways and genes, to further elucidate the pathogenesis of PD. Methods Dataset GSE100054 was downloaded from the Gene Expression Omnibus, and differentially expressed genes (DEGs) in PD samples were identified. Functional enrichment analyses were conducted for the DEGs. The top 10 hub genes in the protein–protein interaction (PPI) network were screened out and used to construct a support vector machine (SVM) model. The expression of the top 10 genes was then validated in another dataset, GSE46129, and a clinical patient cohort. Results A total of 333 DEGs were identified. The DEGs were clustered into two gene sets that were significantly enriched in 12 pathways, of which 8 were significantly deregulated in PD, including cytokine–cytokine receptor interaction, gap junction, and actin cytoskeleton regulation. The signature of the top 10 hub genes in the PPI network was used to construct the SVM model, which had high performance for predicting PD. Of the 10 genes, GP1BA, GP6, ITGB5, and P2RY12 were independent risk factors of PD. Conclusion Genes such as GP1BA, GP6, P2RY12, and ITGB5 play critical roles in PD pathology through pathways including cytokine−cytokine receptor interaction, gap junctions, and actin cytoskeleton regulation.

Regulatory miRNA–mRNA Networks in Parkinson’s Disease

“…In another study, data from Gene Expression Omnibus from patients with PD were used to perform regulatory network and functional and enrichment analysis, showing that distinct pathways, such as amoebiasis and MAPK signaling, might be related to PD [51]. More recently, another study also used a dataset from Gene Expression Omnibus and revealed new 12 pathways associated with PD [52].…”

RNA-seq analysis of gene expression profiles in posttraumatic stress disorder, Parkinson’s disease and schizophrenia identifies roles for common and distinct biological pathways

“…Genes comprising KEGG pathways of Focal adhesion and ECM receptor interaction were found to be enriched in the PD Module 5 but under-expressed in the schizophrenia Module 4. Both pathways have been implicated previously in schizophrenia [99][100][101] and PD [102,103]. Focal adhesions are specialised regions in the cell where it interacts with the extracellular matrix (ECM).…”

Transcriptome Analysis of Induced Pluripotent Stem Cells and Neuronal Progenitor Cells, Derived from Discordant Monozygotic Twins with Parkinson’s Disease

“…Moreover, a direct interaction between NR2F2 and PD was identified. An additional literature analysis identified interactions between those four genes and PD, thereby uncovering a possible connection between P2RY12 and PD [ 28 , 29 ]. Interactions between NR2F2 and P2RY12 and neurons have been also identified.…”

“…Using a meta–analysis of genome-wide association study data, Andersen et al identified a significant association between P2RY12 and PD [ 29 ]. Using machine learning models, Shen et al found that changes in the expression of P2RY12 were a predictor of PD [ 28 ].…”