Causal relationship between Hypertrophic Cardiomyopathy and Psychiatric Disorders: a two-sample Mendelian randomization

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Background: Hypertrophic cardiomyopathy (HCM) is a prevalent genetic cardiovascular disease associated with increased arrhythmia and sudden death risk, especially in young individuals. Mental disorders, such as epilepsy, schizophrenia, Alzheimer's Disease, Parkinson's Disease, and depression, are also influenced by genetic factors. Our study utilizes Mendelian Randomization (MR) to investigate the causal relationship between hypertrophic cardiomyopathy and these mental disorders, shedding light on potential pathogenic links and disease risks. This MR-based analysis offers a novel perspective in exploring these connections. Methods We employed a comprehensive approach to select genetic instrumental variables for hypertrophic cardiomyopathy (HCM), epilepsy, schizophrenia, Alzheimer's Disease, Parkinson's Disease, and depression from different databases. Subsequently, a two-sample Mendelian randomization (MR) analysis was conducted to evaluate causal relationships between HCM and the five psychiatric disorders. We applied appropriate methods based on heterogeneity, including Cochran's Q test and fixed-effects Inverse Variance Weighted (IVW) method. Sensitivity analysis, the maximum likelihood method, was employed to assess causality robustness. Directional pleiotropy was evaluated using the MR-Egger method, and the "leave-one-out" method was applied to gauge individual SNP influence. Results Our analysis identified a promoting effect of depression (fixed effects IVW: p -value = 0.0031, OR = 1.0044, 95% CI=(1.0015, 1.0073)) on HCM. Sensitivity analyses confirmed the reliability of our findings, with no significant heterogeneity or horizontal pleiotropy detected.

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