Abstract
OBJECTIVE: To determine whether a bidirectional causal relationship exists between major depressive disorder (MDD) and heart failure (HF). METHODS: Our two-sample bidirectional Mendelian randomization (MR) study consisted of two parts. In the first part, we conducted a forward MR analysis where MDD was considered as the exposure and HF as the outcome. In the second part, a reverse MR analysis was performed, treating HF as the exposure and MDD as the outcome. Summary data on MDD and HF were obtained from the IEU Open GWAS database. RESULTS: Based on the results of the MR-Egger regression intercept test, there was no evidence of horizontal pleiotropy in this study. Furthermore, the IVW results consistently suggested estimates of causal effect values. The findings revealed that individuals with MDD had a 16.9% increased risk of HF compared to those without MDD (OR = 1.169, 95%CI: 1.044-1.308, P = 0.007). However, there was no evidence to support that HF would increase the risk of MDD (OR = 1.012, 95%CI: 0.932-1.099, P = 0.773). Heterogeneity in SNPs of MDD and HF was observed through the heterogeneity test and funnel plot. Additionally, the leave-one-out method did not identify any instances where a single SNP was biased toward or dependent on causation. CONCLUSION: Our study provides evidence supporting a one-way causal relationship between MDD and HF. Specifically, MDD increases the risk of developing HF. However, our findings did not provide any evidence suggesting that HF increases the risk of developing MDD.