Causal relationship between hypothyroidism and the risk of hearing loss: A bidirectional two-sample Mendelian randomization study

Abstract Background Hypothyroidism's causal direction and the magnitude of its association with hearing loss is uncertain due to the limitations of observational studies. This study aims to investigate the relationship between hypothyroidism and hearing loss using bidirectional two-sample mendelian randomization (MR). Materials and Methods The genetic variants of 462,933 participants in the hypothyroidism study and 323,978 participants in the hearing loss study were used for bidirectional two-sample MR. Independent genetic variants that were significantly ( P < 5×10 − 8 ) associated with each exposure were considered as instruments. To test for sensitivity, Cochran's Q test, the MR-Egger intercept test, and leave-one-out analysis were applied apart from the multiplicative random effects-inverse variance weighted (MRE-IVW) approach used as the main MR analysis. Results The forward MR revealed a significant causal estimate for the genetically predicted hypothyroidism with the high risk of hearing loss [MRE-IVW: odds ratio (OR) = 1.092, P = 0.003]. However, the reverse MR analysis found no significant correlation between genetically predicted hearing loss and hypothyroidism (MRE-IVW: OR = 1.04, P = 0.113). Sensitivity analyses showed that the causal association estimations were stable and reliable. Conclusion In this MR study, we demonstrated hypothyroidism was causally associated with a high risk of hearing loss. However, there was no evidence to support the causality of hearing loss on hypothyroidism.