BACKGROUND: Brugada syndrome (BrS) is associated with an electrocardiogram (ECG), but the causal relationship remains unclear. This study aimed to assess the bidirectional causal relationship between ECG parameters and BrS using Mendelian randomization (MR) analysis. METHODS: A bidirectional MR analysis using data from the OpenGWAS database. Six ECG parameters, including PR interval, PP interval, ST duration, QRS duration, T wave duration, and QT interval, were included in the forward MR analysis with BrS as the outcome. In the reverse MR analysis, BrS was the exposure and the aforementioned ECG parameters were the outcomes. The inverse-variance weighted (IVW) method was the primary analytical approach, complemented by four other methods to account for potential pleiotropy. Sensitivity analyses were performed using Cochran's Q test, MR-Egger intercept, and leave-one-out analysis to evaluate heterogeneity and pleiotropy. RESULTS: In the forward MR, genetically predicted ST duration (OR = 1.3478, 95% CI: 1.0611-1.7118, p = 0.014) and QRS duration (OR = 0.9582, 95% CI: 0.9208-0.9972, p = 0.036) showed significant associations with BrS. The reverse MR indicated that BrS was significantly associated with PR interval, QRS duration, P wave duration, and QT interval (all p <
0.05). Sensitivity analyses confirmed the robustness of the results in both forward and reverse MR analyses. However, there were significant horizontal pleiotropy and heterogeneity in reverse MR analysis. CONCLUSIONS: This MR study supported a causal effect of ECG parameters, including ST duration and QRS duration, on BrS development.