Causal inference in the field of arrhythmia: An introduction to mendelian randomization

Mendelian randomization (MR) uses genetic variants associated with an exposure (eg, high blood pressure) as instrumental variables to test causal effects on an outcome (eg, atrial fibrillation [AF]). By leveraging the random assortment of genetic variants during gamete formation, MR reduces biases like confounding and reverse causation. We screened 391 papers, examining 277 that applied MR to investigate arrhythmia and, in others, cardiovascular traits, lifestyle, behavioral traits, and body composition. Our analysis focused on MR studies of arrhythmia and cardiovascular traits. Key findings highlight high systolic blood pressure, low resting heart rate, elevated cardiac troponin I levels, coronary artery disease, and heart failure as risk factors for AF, whereas AF itself increases heart failure risk. As genetic data become more accessible, MR's relevance grows. Sensitivity analyses and integrating MR with other methodologies in a triangulation framework enhance the robustness of causal inferences by navigating different biases.