Exploring the hub Genes and Potential Mechanisms of Complement system-related Genes in Parkinson Disease: Based on Transcriptome Sequencing and Mendelian Randomization

Abstract

An accurate diagnosis of Parkinson’s disease (PD) remains challenging and the exact cause of the disease is unclean. The aims are to identify hub genes associated with the complement system in PD and to explore their underlying molecular mechanisms. Initially, differentially expressed genes (DEGs) and key module genes related to PD were mined through differential expression analysis and WGCNA. Then, differentially expressed CSRGs (DE-CSRGs) were obtained by intersecting the DEGs, key module genes and CSRGs. Subsequently, MR analysis was executed to identify genes causally associated with PD. Based on genes with significant MR results, the expression level and diagnostic performance verification were achieved to yield hub genes. Functional enrichment and immune infiltration analyses were accomplished to insight into the pathogenesis of PD. qRT-PCR was employed to evaluate the expression levels of hub genes. After MR analysis and related verification, CD93, CTSS, PRKCD and TLR2 were finally identified as hub genes. Enrichment analysis indicated that the main enriched pathways for hub genes. Immune infiltration analysis found that the hub genes showed significant correlation with a variety of immune cells (such as myeloid-derived suppressor cell and macrophage). In the qRT-PCR results, the expression levels of CTSS, PRKCD and TLR2 were consistent with those we obtained from public databases. Hence, we mined four hub genes associated with complement system in PD which provided novel perspectives for the diagnosis and treatment of PD.