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Published on: August 30, 2019
Causal relationship between cardiovascular diseases and vestibular dysfunction: A 2-sample Mendelian randomization
Huiguo Liu1, Liu Shihan, Luo Wenlong
1Department of Otorhinolaryngology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Insights
Cardiovascular diseases like angina, heart failure, and high blood pressure may causally increase the risk of vestibular dysfunction. This genetic study provides evidence for early screening of at-risk individuals.
Area of Science:
- Genetics
- Cardiology
- Neurology
Background:
- Observational studies suggest a link between cardiovascular diseases (CVDs) and vestibular dysfunction.
- The causal mechanisms underlying this association are not well understood.
Purpose of the Study:
- To investigate the potential causal relationship between multiple CVDs and vestibular dysfunction using Mendelian randomization (MR).
- To provide genetic insights into the pathological mechanisms connecting cardiovascular health and vestibular function.
Main Methods:
- Two-sample Mendelian randomization (MR) analysis utilizing large-scale genetic datasets (Genome-Wide Association Study for CVDs and FinnGen database for vestibular dysfunction).
- Employed inverse variance weighting (IVW), MR-Egger, and weighted median methods.
- Conducted sensitivity analyses to assess result robustness and reverse MR to test causality in the opposite direction.
Main Results:
- Genetic evidence supports a causal link between angina pectoris, heart failure, myocardial infarction, high blood pressure, coronary atherosclerosis, and vestibular dysfunction.
- No significant genetic causality was found between atrial fibrillation and vestibular dysfunction.
- Reverse MR analysis did not reveal a causal effect of vestibular dysfunction on CVDs.
Conclusions:
- This study provides the first genetic evidence that several CVDs are risk factors for developing vestibular dysfunction.
- Findings support early clinical screening for vestibular dysfunction in individuals with CVDs.
- Further research into the cardiovascular-vestibular axis molecular mechanisms and interventional studies are warranted for clinical translation.
Abstract:
Observational studies have identified an association between cardiovascular diseases (CVDs) and vestibular dysfunction, but the underlying causal mechanisms remain unclear. This study employs Mendelian randomization (MR) to systematically evaluate, for the first time, the potential causal relationships between multiple CVDs and vestibular dysfunction, providing new insights into the pathological mechanisms involved. Correlations between exposures (atrial fibrillation, angina pectoris, heart failure, myocardial infarction, high blood pressure and coronary atherosclerosis) and outcomes (vestibular dysfunction) were analyzed by 2-sample MR using a dataset of cardiovascular diseases from the Genome-Wide Association Study and a vestibular dysfunction dataset from a FinnGen database (N = 4,08,645) and a reverse MR study was also performed. The inverse variance weighting (IVW) method, MR-Egger method, and weighted median method were chosen, supplemented by various sensitivity analyses to ensure the robustness and reliability of the results. MR analysis showed that angina pectoris (IVW: P = 4.71E-06), heart failure (IVW: P = .017), myocardial infarction (IVW: P = 4.09E-05), high blood pressure (IVW: P = .029), coronary atherosclerosis (IVW: P = 7.76E-07) and vestibular dysfunction were genetically causally associated. However, MR analysis showed no genetic causality between atrial fibrillation and vestibular dysfunction (P = .27). In the reversibility study, no significant associations were found between vestibular dysfunction and outcomes (atrial fibrillation, angina pectoris, heart failure, myocardial infarction, high blood pressure and coronary atherosclerosis) in any of the MR analysis results. Sensitivity analyses showed no horizontal pleiotropy, but there was heterogeneity in some of the results. This study is the first to use MR analysis to demonstrate that multiple CVDs can increase the risk of vestibular dysfunction, providing genetic evidence for early clinical screening of high-risk populations. Future research should further explore the molecular mechanisms, particularly the specific pathways of the cardiovascular-vestibular axis, and conduct interventional studies to validate targeted preventive measures. These findings lay a theoretical foundation for developing novel diagnostic and therapeutic strategies, offering significant potential for clinical translation.
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