Epidermal Growth Factor Receptor Pathway Is a Potential Biological Mechanism in Inflammatory Bowel Disease‐Induced Psoriasis

BACKGROUND AND AIM: Psoriasis and inflammatory bowel disease are characterized by relapsing episodes of immune-mediated, chronic inflammation and frequently co-occur. However, the potential causal relationship between these two conditions and their shared pathogenesis remains unclear. We aimed to explore the pathogenesis and association between psoriasis and inflammatory bowel disease. METHODS: We performed longitudinal cohort analyses using the UK Biobank and additionally incorporated three independent external datasets-the International IBD Genetics Consortium GWAS dataset, the FinnGen psoriasis GWAS dataset, and the plasma proteome dataset reported by Sun et al. to conduct Mendelian randomization and proteomic mediation analyses, thereby investigating the association between inflammatory bowel disease and psoriasis and exploring potential underlying mechanisms. RESULTS: Inflammatory bowel disease increased psoriasis risk in the UK Biobank cohort, as indicated by the Cox model and Mendelian randomization analysis. Smoking, body mass index, and air pollution were identified as risk factors for psoriasis in inflammatory bowel disease patients. In addition, multiple intermediary proteins and their activation pathways were implicated. The epidermal growth factor receptor substrate 15-like 1 was demonstrated as a mediating protein for Crohn's disease and ulcerative colitis in the incidence of psoriasis. Enrichment analysis indicated that the downregulation and signaling of the epidermal growth factor receptor were potential biological mechanisms contributing to the causal relationships between genetic effects and the development of psoriasis and inflammatory bowel disease. CONCLUSION: The epidermal growth factor receptor pathway is a potential mechanism in inflammatory bowel disease-induced psoriasis. This study may inform the clinical management of psoriasis and inflammatory bowel disease.