Shared Genetic Architecture Among Severe Mental Disorders: A System Biology Approach Based on Protein–Protein Interaction

Abstract

Introduction: The study explores shared genetic architecture among major psychiatric disorders—major depressive disorder, bipolar disorder, schizophrenia, and post-traumatic stress disorder—emphasizing their overlapping molecular pathways. Using public datasets, we identified shared genes and examined their functional implications through protein–protein interaction (PPI) networks and gene set enrichment analysis (GSEA). Methods: Genes associated with each disorder were identified through the NCBI Gene database. Intersection analyses of gene sets were conducted using R to identify overlaps among the four disorders. STRING was used to predict PPI and conduct clustering analyses. Gene set enrichment analysis was performed to explore biological pathways, molecular functions, and cellular components. Results: We identified 31 intersected genes across all four disorders. PPI analyses demonstrated significant network enrichment, revealing interconnected pathways related to inflammation, neurotransmission, and synaptic plasticity. Functional enrichment highlighted pathways such as cytokines signaling, dopaminergic transmission, and synaptic vesicle cycling. Tissue expression analysis indicated significant involvement of brain regions, including the anterior cingulate cortex and mesolimbic system. Conclusion: This study underscores the shared genetic underpinnings of severe psychiatric disorders, highlighting common biological processes, such as pro-inflammatory markers and synaptic signaling. These findings offer a transdiagnostic perspective, potentially informing novel therapeutic strategies for overlapping psychiatric conditions.