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

IF 1.1 4区医学 Q4 CARDIAC & CARDIOVASCULAR SYSTEMS Annals of Noninvasive Electrocardiology Pub Date : 2025-03-12 DOI:10.1111/anec.70060

Songcui Shen, Xiaolu Wang, Jingjuan Huang, Wenzhao Li

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Abstract

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.

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背景 Brugada 综合征（BrS）与心电图（ECG）有关，但其因果关系仍不清楚。本研究旨在利用孟德尔随机化（MR）分析法评估心电图参数与 Brugada 综合征之间的双向因果关系。方法利用 OpenGWAS 数据库的数据进行双向 MR 分析。包括 PR 间期、PP 间期、ST 间期、QRS 间期、T 波间期和 QT 间期在内的六个心电图参数被纳入正向 MR 分析，并以 BrS 为结果。在反向 MR 分析中，BrS 为暴露，上述心电图参数为结果。反方差加权（IVW）法是主要的分析方法，并辅以其他四种方法以考虑潜在的多效应。使用 Cochran's Q 检验、MR-Egger 截距和leave-one-out 分析进行了敏感性分析，以评估异质性和多向性。结果在正向 MR 中，遗传预测的 ST 持续时间（OR = 1.3478，95% CI：1.0611-1.7118，p = 0.014）和 QRS 持续时间（OR = 0.9582，95% CI：0.9208-0.9972，p = 0.036）与 BrS 有显著关联。反向 MR 显示，BRS 与 PR 间期、QRS 持续时间、P 波持续时间和 QT 间期显著相关（所有 p 均为 0.05）。敏感性分析证实了正向和反向 MR 分析结果的稳健性。然而，在反向 MR 分析中存在明显的水平多向性和异质性。结论这项磁共振研究支持心电图参数（包括 ST 持续时间和 QRS 持续时间）对 BrS 发展的因果效应。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Annals of Noninvasive Electrocardiology 医学-心血管系统

CiteScore

3.40

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： The ANNALS OF NONINVASIVE ELECTROCARDIOLOGY (A.N.E) is an online only journal that incorporates ongoing advances in the clinical application and technology of traditional and new ECG-based techniques in the diagnosis and treatment of cardiac patients. ANE is the first journal in an evolving subspecialty that incorporates ongoing advances in the clinical application and technology of traditional and new ECG-based techniques in the diagnosis and treatment of cardiac patients. The publication includes topics related to 12-lead, exercise and high-resolution electrocardiography, arrhythmias, ischemia, repolarization phenomena, heart rate variability, circadian rhythms, bioengineering technology, signal-averaged ECGs, T-wave alternans and automatic external defibrillation. ANE publishes peer-reviewed articles of interest to clinicians and researchers in the field of noninvasive electrocardiology. Original research, clinical studies, state-of-the-art reviews, case reports, technical notes, and letters to the editors will be published to meet future demands in this field.