Multi-Modal Analysis of Gene Expression from Postmortem Brains and Blood Identifies Synaptic Vesicle Trafficking Genes to Be Associated with Parkinson's Disease

Objective: We aimed to identify key susceptibility gene targets in multiple datasets generated from post-mortem brains of Parkinson’s disease (PD) patients and healthy controls (HC). Methods: We performed a multi-tiered analysis to integrate the gene expression data using multiple-gene chips from 244 human post mortem tissues. We identified hub node genes in the highly PD-related consensus module by constructing protein-protein interaction (PPI) networks. Next we validated the top four interacting genes in 238 subjects (90 sporadic PD, 125 HC and 23 Parkinson’s Plus Syndrome (PPS)). Utilizing multinomial logistic regression analysis(MLRA) and Receiver Operating Characteristic(ROC), we analyzed the risk factors and diagnostic power for discriminating PD from HC and PPS. Results: We identified 1333 genes that were significantly different between PD and HCs based on seven microarray datasets. The identified MEturquoise module is related to synaptic vesicle trafficking (SVT) dysfunction in PD (P