Investigating Causal Associations Between Circulating Cytokines and Vestibular Disorders Using Mendelian Randomization: Insights from Large-Scale Genome-Wide Association Studies Data in European Populations

The presence of circulating cytokines has a significant impact on the development and progression of vestibular disorders. However, further investigation is needed to determine the direction of causation and causal effects. By applying two-sample Mendelian randomization (MR), we analyzed the potential causal connection between 41 circulating cytokines and vestibular disorders using the integrated data from genome-wide association studies (GWAS). The major analysis utilized for MR was inverse variance weighted (IVW). To examine reverse causation, we conducted reverse MR analysis. In addition, we assessed the robustness of the findings by performing pleiotropy and heterogeneity tests. Our results demonstrated that two circulating cytokines were significantly correlated with vestibular disorders risk. More specifically, vascular endothelial growth factor [IVW, odds ratio (OR) = 0.999, 95% confidence interval (CI) = 0.999-1.000, <i>P</i> = 0.046] and interleukin-7 (IVW, OR = 0.999, 95% CI = 0.998-1.000, <i>P</i> = 0.033) were negatively correlated with vestibular disorders risks, respectively. No evidence was identified to support associations between the remaining 39 circulating cytokines and vestibular disorders. These findings reveal a distinct correlation between circulating cytokines and vestibular diseases, providing a novel perspective and potential biological target for future clinical interventions for vestibular disorders.