Causal relationship between moderate to vigorous physical activity and venous thromboembolism

Previous studies have shown conflicting results about the impact of moderate to vigorous physical activity on the risk of venous thromboembolism (VTE).  Using Mendelian randomization, we assessed whether moderate to vigorous physical activity causally affects VTE from genetic level. Genetic instruments associated with moderate to vigorous physical activity at the genome-wide significance level (P < 5×10^- 8) were selected from the UK Biobank. Summary-level data for VTE were obtained from the FinnGen consortium. Univariable and multivariable Mendelian randomization analyses were conducted. Genetically predicted moderate to vigorous physical activity had no effect on VTE [odds ratio (OR) = 1.08; 95% confidence interval (CI) 0.66-1.78; P = 0.75] under a multiplicative random-effects inverse-variance weighted model. MR-Egger (OR = 0.20; 95% CI 0.01-4.70; P = 0.33), weighted median (OR = 1.08; 95% CI 0.52-2.25; P = 0.84), simple mode (OR = 2.53; 95% CI 0.59-10.92; P = 0.23), weighted mode (OR = 2.21; 95% CI 0.50-9.74; P = 0.31), and multivariable Mendelian randomization (OR = 0.74; 95% CI 0.46-1.19; P = 0.22) also yielded no significant association. The overall estimate was not influenced by individual single nucleotide polymorphism. No evidence of heterogeneity or horizontal pleiotropy was observed. Therefore, moderate to vigorous physical activity had no causal association with VTE in the general population.