Exploration of the potential causative genes for inflammatory bowel disease: Transcriptome-wide association analysis, Mendelian randomizzation analysis and Bayesian colocalisation

Background Inflammatory bowel disease (IBD) poses a complex challenge due to its intricate underlying mechanisms, and curative treatments remain elusive. Consequently, there is an urgent need to identify genes causally associated with IBD. Methods We extracted blood eQTL data from the GTExv8.ALL.Whole_Blood database, genome-wide association studies (GWAS) summary statistics of IBD from the IEU GWAS database, and performed a three-fold analysis protocol, including transcriptome-wide association analysis, Mendelian randomisation analysis, Bayesian colocalisation, and subsequent potential therapeutic agents identification. Results We identified four pathogenic genes, namely CARD9, RTEL1, STMN3 and ARFRP1, that promote the development of IBD, encompassing both ulcerative colitis (UC) and Crohn's disease (CD). Notably, ARFRP1 exhibited the ability to suppress IBD (encompassing UC and CD) development. Regarding drug prediction, cyclophosphamide emerged as a promising novel therapeutic option for IBD, encompassing UC and CD. Conclusion We identified several potential genes related to IBD (UC and CD), including CARD9, RTEL1, STMN3 and ARFRP1, warranting further investigation in functional studies to elucidate underlying disease mechanisms. Additionally, clinical studies exploring the potential of cyclophosphamide as a treatment avenue for IBD are warranted.