Exploring the Causal Effects of Physical Activity, Sedentary Behaviour, and Diet on Atrial Fibrillation and Heart Failure: A Multivariable Mendelian Randomisation Analysis

Abstract

Aims: This study aimed to investigate the causal effects of physical activity, sedentary behaviour, and diet on atrial fibrillation (AF) and heart failure (HF) using multivariate Mendelian randomization (MR) analysis and genetic variants as instrumental variables. Methods: The study employed multivariate MR analysis with physical activity, sedentary behaviour, and diet as exposures and AF and HF as outcomes. Data were obtained from the UK Biobank (over 500,000 participants) and the FinnGen project (218,792 participants of European ancestry). Genetic variants associated with physical activity, diet, and sedentary behaviour were used as instrumental variables. The main analysis methods included the inverse variance weighted (IVW) method, MR-Egger, and weighted median methods. Heterogeneity was assessed using Cochran’s Q test. Results: The analyses generally did not demonstrate significant causal relationships between physical activity or sedentary behaviour and AF. Diet showed a potential protective effect on AF in some analyses but was not consistently significant across methods. For HF, physical activity and sedentary behaviour did not show significant causal relationships. Diet showed a significant protective effect against HF in the IVW method but was not consistent across all methods. Conclusions: This study suggests that while there may be some protective effects of these lifestyle factors on cardiovascular disease, most analyses did not show significant causality, and results were inconsistent. Further research is needed to validate these findings.