Identification of overlapping genetic loci between inflammatory bowel disease and major depressive disorder.

BACKGROUND: Patients diagnosed with inflammatory bowel disease (IBD) are often observed to suffer from co-occurring major depressive disorder (MDD). Although the precise mechanisms remain elusive, there is a possibility of a genetic overlap between these conditions. METHODS: Genome-wide association study data collected from two IBD cohorts alongside one MDD cohort were analyzed. Initially, linkage disequilibrium score regression, genetic covariance analysis, and high-definition likelihood estimation was applied to explore the overall correlation between the diseases. Local genetic correlations were subsequently assessed through heritability estimation derived from summary statistics. Following this, genetic overlap analysis was conducted based on the conditional/conjunctional false discovery rate (cond/conjFDR) statistical model, identifying shared genetic genes across various traits. RESULTS: On a genome-wide scale, significant correlations, both overall and local, were observed between IBD (including Crohn’s disease and ulcerative colitis) and MDD. Genetic overlap between the two disorders was confirmed through conjFDR analysis, which also pinpointed relevant genetic risk genes. Ten specific genes, namely RBMS1, C3orf84, AC008703.1, ZNF365, MED24, TCF4, CRB1, CCSER1, P4HA2, and RASGRP1, emerged as noteworthy. Additionally, these genes exhibited enrichment in pathways related to synaptic transmission. CONCLUSION: This investigation presents genetic evidence supporting the comorbidity of IBD and MDD, thereby contributing to a deeper understanding of the pathophysiological connections between these conditions.