肥胖相关特征部分介导阻塞性睡眠呼吸暂停对静脉血栓栓塞风险的影响

文献信息

中文摘要

背景： 尽管观察性研究提示阻塞性睡眠呼吸暂停（OSA）与血栓栓塞之间存在关联，但因果证据仍有待确立。
方法： 采用连锁不平衡评分回归（LDSC）评估OSA与血栓栓塞之间的遗传相关性。基于LDSC结果，进行两样本孟德尔随机化（MR）分析，以探究OSA与血栓栓塞特征（如静脉血栓栓塞（VTE）、肺栓塞（PE）、深静脉血栓形成（DVT）以及静脉炎和血栓性静脉炎（不包括DVT）（PT））之间的因果关系，包括反向关联。除贝叶斯加权MR分析外，还应用了四种常用MR方法评估因果关系。在调整潜在混杂因素（包括久坐行为（如驾驶、使用电脑、看电视）、吸烟和饮酒）后，进行多变量分析。进行中介分析以评估肥胖相关特征的中介作用。
结果： LDSC识别出OSA与血栓栓塞亚型（VTE、PE和PT）之间的遗传相关性。单变量MR表明，OSA在遗传上预测VTE、PE和PT风险增加，未发现显著反向因果关系的证据。调整混杂因素后，OSA仍与这些特征显著相关。中介分析显示，OSA对血栓栓塞的影响部分由肥胖相关特征介导。
结论： 本研究确定了OSA与特定血栓栓塞亚型之间存在正向因果关联，未发现反向因果关系的证据。肥胖可能部分介导OSA对血栓栓塞的影响。

英文摘要

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.