Genetic Overlap Between Inflammatory Bowel Disease and Neurological Disorders: Insights from GWAS and Gene Expression Analysis

Abstract

Inflammatory Bowel Disease (IBD), which includes Crohn's disease (CD) and Ulcerative Colitis (UC), is a complex and multifactorial condition marked by chronic inflammation of the gastrointestinal tract. This study leverages data from genome-wide association studies (GWAS) and gene expression data from the Genotype-Tissue Expression (GTEx) project to investigate the genetic and expression profiles of IBD and its subtypes. We examined 207 studies related to IBD, 71 specific to CD, and 66 focused on UC, identifying both shared and unique genetic factors among these conditions. GWAS meta-analysis revealed the top IBD associated genes that include IL23R, NOD2, ATG16L1, HLA-DRB9, and more. Pathway enrichment analyses identified consistently enriched pathways such as the NF-kappa B signaling pathway, JAK-STAT signaling pathway, and cytokine-cytokine receptor interaction, all of which play critical roles in immune responses and inflammation. Gene Ontology (GO) term analysis highlighted processes like cytokine production, cell activation, and leukocyte activation, reinforcing their involvement in the pathogenesis of IBD. Gene expression analysis showed that genes associated with IBD are expressed not only in the gastrointestinal tract but also in various regions of the brain, suggesting potential links between IBD and neurological functions. Our study further explored the genetic overlap between IBD and several neurological disorders, including schizophrenia, depression, autism spectrum disorder, and attention-deficit/hyperactivity disorder, uncovering a shared genetic architecture. These findings emphasize the systemic nature of IBD and its potential neurological implications, paving the way for targeted therapeutic strategies that address both gastrointestinal and neurological aspects of the disease.