Major depression disorder may have no causality on the atrial fibrillation risk: Evidence from the Mendelian randomization study

Abstract Background: Accumulated studies have indicated that depression was significantly associated with the atrial fibrillation (AF) risk. However, the causal effect of major depressive disorder (MDD) on the risk of AF was elusive. Methods: We performed a two-sample Mendelian randomization (MR) analysis using two genetic instrument tools for MDD to assess the potential causal effect of MDD on the AF risk, including a training dataset (37 single-nucleotide polymorphisms (SNPs) significantly associated with MDD) and a validation dataset (11 SNPs robustly associated with MDD). Inverse-variance weighted method (IVW), weighted median method, MR-Egger, MR-Pleiotropy REsidual Sum and Outlier (MR-PRESSO) test, pleiotropy test, and leave-one-out sensitivity analysis were performed for MR analyses. Results: We first performed MR analysis for a training data using multiple data processing steps, including removing SNPs related with AF risk factors, removing one outlier with MR-PRESSO, and tighten instrument P value threshold. The final MR estimates suggested that MDD had no causality on AF incidence (IVW method, OR = 1.04, 95%CI = 0.79–1.36, P value = 0.785; weighted median, OR = 1.15, 95%CI = 0.90–1.46, P value = 0.268; MR-Egger, OR = 1.00, 95%CI = 0.35–2.85, P value = 0.999). Moreover, a consistent result was displayed in MR estimates using a validation data. Pleiotropy test and leave-one-out sensitivity analysis revealed that our results were robust. Conclusions: Our MR analysis suggested that MDD may have no causality on the AF risk.