Obesity-Related Traits Partially Mediate the Impact of Obstructive Sleep Apnea on the risk of Venous Thromboembolism.

BACKGROUND: Although observational studies have suggested an association between obstructive sleep apnea (OSA) and thromboembolism, causal evidence remains to be established. METHODS: Linkage disequilibrium score regression (LDSC) was used to evaluate the genetic correlations between OSA and thromboembolism. Based on the results of LDSC, two-sample Mendelian randomization (MR) analyses were performed to investigate the causal relationships between OSA and thromboembolism traits, such as venous thromboembolism (VTE), pulmonary embolism (PE), deep vein thrombosis (DVT), and phlebitis and thrombophlebitis (not including DVT) (PT), including reverse associations. Four common MR methods, in addition to Bayesian weighted MR analysis, were applied to evaluate causality. Multivariable analyses were conducted after adjustment for potential confounders, including sedentary behaviors (e.g., driving, computer use, TV viewing), smoking, and alcohol consumption. Mediation analysis was performed to assess the mediating role of obesity-related traits. RESULTS: LDSC identified genetic correlations between OSA and thromboembolic subtypes (VTE, PE, and PT). Univariate MR indicated that OSA genetically predicted an increased risk of VTE, PE, and PT, with no evidence of significant reverse causality. After adjusting for confounders, OSA remained significantly associated with these traits. Mediation analyses revealed that the effect of OSA on thromboembolism was partially mediated by obesity-related traits. CONCLUSION: This study identified a positive causal association between OSA and specific thromboembolic subtypes, with no evidence of reverse causality. Obesity may partially mediate the effect of OSA on thromboembolism.