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

Qinghua Luo; Jiawen Wang; Wei Ge; Zihao Li; Yuanting Mao; Chen Wang; Leichang Zhang

doi:10.1016/j.heliyon.2024.e28944

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

Heliyon. 2024 Apr 6;10(7):e28944. doi: 10.1016/j.heliyon.2024.e28944. eCollection 2024 Apr 15.

Authors

Qinghua Luo¹, Jiawen Wang², Wei Ge³, Zihao Li⁴, Yuanting Mao¹, Chen Wang², Leichang Zhang⁵

Affiliations

¹ Clinical Medical College, Jiangxi University of Chinese Medicine, Nanchang, China.
² Department of Proctology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
³ Department of Proctology, Affiliated Hospital of Jiangxi University of Chinese Medicine, Nanchang, China.
⁴ Office of the President, Jiangmen Wuyi Hospital of Traditional Chinese Medicine, Jiangmen, China.
⁵ Formula-Pattern Research Center, Jiangxi University of Chinese Medicine, Jiangxi, China.

Abstract

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.