Exploring the Association Between Mental Disorders and Various Arrhythmias via Mendelian Randomization Methods

Major depression, bipolar disorder, and schizophrenia are common mental illnesses, and their potential association with arrhythmias has long been a focus of clinical and research interest. To explore the possible causal relationship between these mental disorders and arrhythmias, we conducted a bidirectional two-sample Mendelian randomization (MR) analysis using publicly available GWAS summary statistics. The primary analysis employed the inverse-variance weighted (IVW) method, with sensitivity analyses including MR-Egger regression and the weighted median estimator to assess robustness and address potential pleiotropy. Results indicated that genetic predisposition to major depression was associated with increased risks of atrial fibrillation/flutter (IVW: OR = 1.214, 95% CI: 1.092-1.349, p < 0.001), paroxysmal tachycardia (IVW: OR = 1.493, 95% CI: 1.261-1.769, p < 0.001), and atrioventricular block (IVW: OR = 1.257, 95% CI: 1.147-1.377, p < 0.001). Reverse MR also suggested a modest effect of atrioventricular block on depression risk (IVW: OR = 1.045, 95% CI: 1.011-1.079, p = 0.008). In conclusion, from the perspective of genetic liability and using the MR framework, our analysis supports a causal role of major depression in increasing the risk of several arrhythmias and suggests potential bidirectional causal effects between depression and atrioventricular block.