[Inflammatory bowel disease increases the risk of hearing loss via autoimmunity: a Mendelian randomization study]

Objective: This study investigates the intriguing causal relationship between inflammatory bowel disease (IBD) and the risk of hearing loss (HL). Furthermore, an attempt was made to quantify the role of immunization as a potential mediator. Methods: Our research process was meticulously designed and executed. We pooled data from gene-wide association studies (GWAS) obtained IBD data from the European IEU database (website: https://gwas.mrcieu.ac.uk/) and GWAS data for HL from the Finnish database (website: https://www.finngen.fi/fi). We then applied a range of rigorous statistical methods, including the inverse-variance weighted (IVW) method, Mendelian randomization (MR)-Egger regression method, weighted median (WME), simple mode (SM), and weighted mode (WM), to perform two-sample MR analysis and to evaluate a causal relationship of IBD on HL risk in terms of odds ratio (OR) and 95% confidence interval (CI). We also conducted Cochran's Q heterogeneity test by IVW and MR-Egger regression, respectively, and multiple validity test by MR_pleiotropy_test function, MR PRESSO, and sensitivity analysis by MR_leaveoneout_plot function, and F-values were computed to assess the presence of weak instrumental variable bias. Results: The IVW analysis indicated that IBD was a risk factor for HL (OR: 1.055, 95%CI: 1.006-1.105, P=0.026). Furthermore, the analysis demonstrated a causal relationship between IBD and autoimmunity (OR: 1.008, 95%CI: 1.005-1.010, P<0.001). In addition, autoimmunity was found to be a risk factor for HL (OR: 2.822, 95%CI: 1.115-7.142, P=0.029). In the mediation analysis, the direct effect was not significant (95%CI:-0.002-0.092, P=0.062), while, the indirect effect was significant (95%CI:<0.001-0.015, P=0.048). Conclusions: IBD has been demonstrated to heighten the probability of developing HL through the action of autoimmunity-mediated mechanisms.