Weighted Gene Coexpression Network Analysis Uncovers Critical Genes and Pathways for Multiple Brain Regions in Parkinson's Disease

OBJECTIVE: In this study, we aimed to identify critical genes and pathways for multiple brain regions in Parkinson's disease (PD) by weighted gene coexpression network analysis (WGCNA). METHODS: From the GEO database, differentially expressed genes (DEGs) were separately identified between the substantia nigra, putamen, prefrontal cortex area, and cingulate gyrus of PD and normal samples with the screening criteria of p value < 0.05 and ∣log(2)fold change (FC) | >0.585. Then, a coexpression network was presented by the WGCNA package. Gene modules related to PD were constructed. Then, PD-related DEGs were used for construction of PPI networks. Hub genes were determined by the cytoHubba plug-in. Functional enrichment analysis was then performed. RESULTS: DEGs were identified for the substantia nigra (17 upregulated and 52 downregulated genes), putamen (317 upregulated and 317 downregulated genes), prefrontal cortex area (39 upregulated and 72 downregulated genes), and cingulate gyrus (116 upregulated and 292 downregulated genes) of PD compared to normal samples. Gene modules were separately built for the four brain regions of PD. PPI networks revealed hub genes for the substantia nigra (SLC6A3, SLC18A2, and TH), putamen (BMP4 and SNAP25), prefrontal cortex area (SNAP25), and cingulate gyrus (CTGF, CDH1, and COL5A1) of PD. These DEGs in multiple brain regions were involved in distinct biological functions and pathways. GSEA showed that these DEGs were all significantly enriched in electron transport chain, proteasome degradation, and synaptic vesicle pathway. CONCLUSION: Our findings revealed critical genes and pathways for multiple brain regions in PD, which deepened the understanding of PD-related molecular mechanisms.