Association of triglyceride and cholesterol with vestibular vertigo: Evidence from univariable and multivariable mendelian randomization and mediation analysis

OBJECTIVES: This study aimed to use Mendelian Randomization (MR) method to explore the potential causal association of triglyceride and cholesterol on the risk of vestibular vertigo and potential mediating factors. METHODS: We extracted genetic variants associated with triglyceride and cholesterol from the genome-wide association study. Univariable two-sample MR were performed to evaluate the effects of triglyceride and cholesterol on the vestibular vertigo. Besides, Multivariate MR (MVMR) was used to estimate direct effects of triglyceride and cholesterol on the vestibular vertigo after adjusting for potential mediating factors. We also performed that a two-step mediation MR framework to elucidate potential mediators and to estimate the proportion of the association mediated. RESULTS: Genetically predicted triglyceride and cholesterol were positively associated with the risk of vestibular vertigo. In the MVMR analysis, causal associations between triglyceride and cholesterol with vestibular vertigo remained stable and robust after adjusting for body mass index, hypertension, and type 2 diabetes, whereas the association between triglyceride and cholesterol and the risk of vestibular vertigo became nonsignificant after adjusting for vitamin D. In the mediation analysis, we found that the causal effect of cholesterol on vestibular vertigo might partly mediated by vitamin D. CONCLUSION: The present study provides robust evidence that genetically predicted triglyceride and cholesterol are independently causally associated with the risk of vestibular vertigo. Vitamin D also was found to mediate the causal pathways between cholesterol and vestibular vertigo. LEVEL OF EVIDENCE: Level III.