Causal Relationship Between Electrocardiogram Parameters and Brugada Syndrome: A Bidirectional Mendelian...

Area of Science:

• Cardiology
• Genetics
• Epidemiology

Background:

• Brugada syndrome (BrS) is linked to electrocardiogram (ECG) abnormalities, but the causal relationship is not fully understood.
• Investigating the bidirectional causality between ECG parameters and BrS is crucial for understanding disease mechanisms.

Purpose of the Study:

• To assess the bidirectional causal relationship between specific ECG parameters and Brugada syndrome using Mendelian randomization (MR).

Main Methods:

• A bidirectional MR analysis was conducted using data from the OpenGWAS database.
• Six ECG parameters (PR, PP, ST, QRS, T wave, and QT intervals) were analyzed in relation to BrS.
• Inverse-variance weighted (IVW) method was primary, with sensitivity analyses for pleiotropy and heterogeneity.

Main Results:

• Forward MR indicated genetically predicted ST duration and QRS duration are significantly associated with BrS.
• Reverse MR showed BrS is significantly associated with PR interval, QRS duration, P wave duration, and QT interval.
• Sensitivity analyses confirmed result robustness, though reverse MR analysis revealed heterogeneity and pleiotropy.

Conclusions:

• The MR study provides evidence supporting a causal effect of ECG parameters, specifically ST duration and QRS duration, on the development of Brugada syndrome.
• These findings highlight the potential role of specific ECG waveform characteristics in the pathogenesis of BrS.