Inflammatory bowel disease and hearing loss: A study of Mendelian randomization

This study explored the intriguing causal relationship between inflammatory bowel disease (IBD) and risk of hearing loss (HL). Here, we aimed to quantify the role of autoimmunity as a potential mediator. We pooled data from genome-wide association studies (GWAS) for ulcerative colitis (UC), Crohn disease (CD), and autoimmunity from the European IEU database and genome-wide association studies (GWAS) for HL from the Finnish database. We then applied a range of rigorous statistical methods, including inverse-variance weighted (IVW), Mendelian randomization Egger regression (MR-egger), weighted median (WME), simple mode (SM), and weighted mode (WM), to perform Mendelian randomization analysis and evaluate the causal relationship between IBD and HL risk using odds ratios (OR) and 95% confidence intervals (CI). We also conducted Cochran Q heterogeneity test using IVW and MR-Egger regression (MR-egger), and multiple validity tests using Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO), and sensitivity analysis using the MR_leaveoneout_plot function. F -values were computed to assess the presence of weak instrumental variable bias. IVW results showed that in the classification of IBD, not only CD was a risk factor for HL [OR: 1.045, 95%CI: 1.007–1.086, P = .019], but UC was also a risk factor for HL [OR:1.370, 95%CI: 1.027–1.828, P = .031]. CD was a risk factor for autoimmunity [OR: 1.005, 95%CI: 1.003–1.008, P < .001], UC was a risk factor for autoimmunity [OR: 1.092, 95%CI: 1.051–1.135, P < .001], and autoimmunity was also a risk factor for HL [OR: 2.898, 95%CI: 1.048–8.009, P = .040]. However, the relationship between CD and HL ( P = .127) or between UC and HL ( P = .083) was not mediated by autoimmunity. The risk of HL is directly increased by CD and UC. The role of autoimmunity in this process is not a mediating factor.