Graduate School of Guangxi University of Chinese Medicine, Nanning, China.
Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, China.
Thromb Haemost. 2024 Aug;124(8):795-802. doi: 10.1055/s-0044-1781425. Epub 2024 Feb 22.
Given the current debate in clinical research about the relationship between tobacco smoking and the risk of venous thromboembolism (VTE), a Mendelian randomization (MR) study was conducted aimed at elucidating the causal associations of current and past tobacco smoking with the risk of VTE, from the perspective of genetics.
Two-sample univariate and multivariable MR analyses were designed, using summary-level data from large genome-wide association studies involving European individuals. Causality was primarily assessed using multiplicative fixed-effects or random-effects model and inverse variance weighting, supplemented by MR-Egger regression, MR-PRESSO, Cochran's Q test, and leave-one-out for sensitivity analysis to test the reliability of the results.
In the univariate MR analysis, no significant causal effects were found between current tobacco smoking and the risk of VTE, deep vein thrombosis (DVT), and pulmonary embolism (PE). Similarly, no significant causal effects were found between past smoking and VTE, DVT, and PE. As for the multivariable MR analysis, results were consistent with univariate MR analysis, with no significant causal effect of either current or past tobacco smoking on the risk of VTE, DVT, and PE.
Evidence from both univariate and multivariable MR analyses demonstrated no significant causal relationships between current and past tobacco smoking and VTE, DVT, and PE. This contradicts positive correlations reported in some previous observational studies, which may be explained by other confounding factors. This provided genetic evidence for the conclusion reported in other observational studies that smoking did not affect VTE risk.
鉴于目前临床研究中关于吸烟与静脉血栓栓塞症（VTE）风险之间的关系存在争议，本项孟德尔随机化（MR）研究旨在从遗传学角度阐明当前和既往吸烟与 VTE、深静脉血栓形成（DVT）和肺栓塞（PE）风险之间的因果关联。
采用两样本单变量和多变量 MR 分析设计，使用涉及欧洲人群的大型全基因组关联研究的汇总水平数据。主要使用乘法固定效应或随机效应模型和逆方差加权来评估因果关系，并辅以 MR-Egger 回归、MR-PRESSO、Cochran's Q 检验和逐一剔除敏感性分析，以测试结果的可靠性。
在单变量 MR 分析中，当前吸烟与 VTE、DVT 和 PE 风险之间未发现显著的因果关系。同样，既往吸烟与 VTE、DVT 和 PE 之间也未发现显著的因果关系。对于多变量 MR 分析，结果与单变量 MR 分析一致，当前或既往吸烟与 VTE、DVT 和 PE 风险之间均无显著的因果关系。
单变量和多变量 MR 分析的证据均表明，当前和既往吸烟与 VTE、DVT 和 PE 之间无显著的因果关系。这与一些先前观察性研究报告的阳性相关性相矛盾，这可能是由其他混杂因素解释的。这为其他观察性研究报告的吸烟不会影响 VTE 风险的结论提供了遗传证据。
