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阻塞性睡眠呼吸暂停与静脉血栓栓塞症的关联:一项双向两样本 Mendelian Randomization 研究。

The Association between Obstructive Sleep Apnea and Venous Thromboembolism: A Bidirectional Two-Sample Mendelian Randomization Study.

机构信息

Emergency Medicine Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China.

Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China.

出版信息

Thromb Haemost. 2024 Nov;124(11):1061-1074. doi: 10.1055/a-2308-2290. Epub 2024 Apr 17.

Abstract

BACKGROUND

Despite previous observational studies linking obstructive sleep apnea (OSA) to venous thromboembolism (VTE), these findings remain controversial. This study aimed to explore the association between OSA and VTE, including pulmonary embolism (PE) and deep vein thrombosis (DVT), at a genetic level using a bidirectional two-sample Mendelian randomization (MR) analysis.

METHODS

Utilizing summary-level data from large-scale genome-wide association studies in European individuals, we designed a bidirectional two-sample MR analysis to comprehensively assess the genetic association between OSA and VTE. The inverse variance weighted was used as the primary method for MR analysis. In addition, MR-Egger, weighted median, and MR pleiotropy residual sum and outlier (MR-PRESSO) were used for complementary analyses. Furthermore, a series of sensitivity analyses were performed to ensure the validity and robustness of the results.

RESULTS

The initial and validation MR analyses indicated that genetically predicted OSA had no effects on the risk of VTE (including PE and DVT). Likewise, the reverse MR analysis did not find substantial support for a significant association between VTE (including PE and DVT) and OSA. Supplementary MR methods and sensitivity analyses provided additional confirmation of the reliability of the MR results.

CONCLUSION

Our bidirectional two-sample MR analysis did not find genetic evidence supporting a significant association between OSA and VTE in either direction.

摘要

背景

尽管先前的观察性研究表明阻塞性睡眠呼吸暂停(OSA)与静脉血栓栓塞症(VTE)之间存在关联,但这些发现仍存在争议。本研究旨在通过双向两样本 Mendelian 随机化(MR)分析,从遗传水平上探讨 OSA 与 VTE(包括肺栓塞[PE]和深静脉血栓形成[DVT])之间的关联。

方法

利用欧洲人群中大规模全基因组关联研究的汇总水平数据,我们设计了双向两样本 MR 分析,全面评估 OSA 与 VTE 之间的遗传关联。MR 分析的主要方法为逆方差加权法。此外,还使用了 MR-Egger、加权中位数和 MR 多效性残差和异常值(MR-PRESSO)进行补充分析。此外,还进行了一系列敏感性分析,以确保结果的有效性和稳健性。

结果

初步和验证性 MR 分析表明,遗传预测的 OSA 对 VTE(包括 PE 和 DVT)的风险没有影响。同样,反向 MR 分析也没有发现 VTE(包括 PE 和 DVT)与 OSA 之间存在显著关联的实质性证据。补充的 MR 方法和敏感性分析进一步证实了 MR 结果的可靠性。

结论

我们的双向两样本 MR 分析没有发现遗传证据支持 OSA 与 VTE 之间存在显著关联。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/689d/11518617/4bda17be835e/10-1055-a-2308-2290-i23110519-1.jpg

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