Integrative eQTL and Mendelian Randomization Analyses with Experimental Validation Prioritize Genetic Candidate Biomarkers for Crohn’s Disease

INTRODUCTION: Crohn's disease (CD) is a chronic, idiopathic inflammatory bowel disease. Understanding the genetic and immunological basis of CD can lead to better therapeutic strategies. METHODS: We employed publicly available datasets from the Gene Expression Omnibus (GEO) database to identify instrumental variables through expression quantitative trait loci (eQTL) analysis and conducted two-sample Mendelian randomization (MR) analyses. Additionally, we investigated the functions and pathways of co-expressed genes using GO, KEGG, and GSEA analyses. The association between these genes and immune cells was examined through immune cell infiltration assessment. Finally, the co-expressed genes were validated. RESULTS: Several genes, including BATF2, SERPINB9, FCGR2A, MCTP1, SNX30, and SMIM1, were identified as having a causal relationship with CD. These genes are involved in important biological processes and pathways, including autoimmune regulation and oxidative stress. Moreover, CIBERSORT analysis demonstrated a unique distribution of immune cells in CD. Monocytes were significantly decreased in the disease group's tissues. Immune cell infiltration analysis further emphasized the distinct immune landscapes within this disease. DISCUSSION: This study identified key genes associated with Crohn's disease, involving immune regulation and other factors, supplementing existing research. Despite limitations such as reliance on public data and insufficient experimental validation, the results provide a basis for exploring potential targets and conducting in-depth mechanism studies. CONCLUSION: The results of our study on the molecular mechanism of CD offer new insights into the identification of key genetic traits and potential therapeutic targets, which will enhance our understanding of the disease and lead to the development of more effective treatment options.