Association between body mass index and electrocardiogram indices: A Mendelian randomization study

Introduction: Cardiovascular diseases (CVDs) remain a global health concern, and body mass index (BMI) is known to be associated with an increased risk of CVD, but the exact mechanisms underlying this relationship remain unclear. This study employs Mendelian randomization (MR) to investigate the causal association between BMI and electrocardiogram (ECG) indices, providing insights into potential pathways linking obesity to CVD. Methods: We conducted a comprehensive MR study utilizing large-scale genetic and ECG data from diverse populations. Instrumental variables were selected from genome-wide association studies, ensuring their relevance to BMI. Causal relationships between BMI and ECG indices, including P wave duration, PR interval, QRS duration, and QT interval, were assessed using various MR methods, with inverse variance weighted (IVW) considered as the primary analysis. Results: Our MR analysis revealed a significant positive causal association between higher BMI and P wave duration (beta = 8.078, 95% CI: 5.322 to 10.833, p < 0.001), suggesting a potential mechanism through which higher BMI may contribute to arrhythmogenic risks. However, no significant causal associations were observed between BMI and PR interval, QRS duration, or QT interval (all p > 0.005). In addition, our study also found that there is no horizontal pleiotropy between BMI and P wave duration, PR interval, QRS duration, and QT interval, suggesting that the conclusions of this study are robust. Conclusion: This study supports a causal relationship between elevated BMI and prolonged P wave duration, a marker of increased atrial arrhythmogenic risk. Further investigations are still needed to elucidate the underlying mechanisms.