Abstract
BACKGROUND: Major depressive disorder (MDD) is a serious mental health problem in modern society, which is difficult to identify and diagnose in the early stages. Despite strong evidence supporting the heritability of MDD, progresses in large-scale and individual genetic studies remain preliminary. METHODS: In this study, a multi-data source-based prioritization (MDSP) method was proposed, and an appropriate threshold was determined for the optimization of depression-related genes (DEPgenes). Analyses on Gene Ontology biological processes, KEGG pathway and the specific pathway crosstalk network were further proposed. RESULTS: A total of 143 DEPgenes were identified and the MDD-specific network was constructed for the pathogenesis investigation and therapeutic methods development of MDD. Comparing with existing research strategies, the genetic optimization and analysis results were confirmed to be reliable. Finally, the pathway enrichment and crosstalk analyses revealed two unique pathway interaction modules that were significantly enriched with MDD genes. The related core pathways of neuroactive ligand-receptor interaction and dopaminergic synapse supported the neuropathology hypothesis of MDD. And the pathways of serotonergic synapse and morphine addiction indicated the mechanism of drug addiction caused by serotonin used in the treatment. CONCLUSIONS: This work provided a reference for the study of MDD, although future validation by extensive experimentation is still required.