Among Men, Testosterone Levels Associated with Increased Risk of IBD: a Two-sample Mendelian Randomization Study

Abstract Introduction Although observational studies have shown an association between testosterone (T) and inflammatory bowel disease (IBD), the correlation remains controversial. In this study, we aimed to explore the potential causal relationship between T and IBD among men. Methods We utilized two-sample Mendelian randomization (MR) to investigate the causal relationship between testosterone and IBD among men using SNPs as genetic instrumental variables for exposure and outcome. The two-sample Mendelian randomization methods we used included inverse variance weighted (IVW) and MR‒Egger regression. Odds ratios (ORs) were applied to evaluate the results. Results A total of 112 SNPs were included in the MR study. The causal relationship between exposure factors and outcomes was derived using the two-sample Mendelian randomization method. The results of MR analysis demonstrated that testosterone among men was associated with an increased risk of inflammatory bowel disease (β=0.146 [OR 1.157 95% CI 1.102, 2.568], p=0.022, IVW), and MR‒Egger tests also supported this conclusion. (0.196[1.218 0.968, 1.534]0.095) The Cochran Q tests indicated that there was heterogeneity but not horizontal pleiotropy of SNPs, so we believe that the results remain robust. Conclusion This MR analysis provided evidence that testosterone was causally responsible for IBD among men, indicating that heterogeneous therapeutic measurements should be taken between male and female.