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经典血液脂质与静脉血栓形成的双向孟德尔随机研究。

A bidirectional Mendelian randomized study of classical blood lipids and venous thrombosis.

机构信息

Department of Joint Surgery, HongHui Hospital, Xi'an Jiaotong University, Xi'an, 710054, Shaanxi, China.

出版信息

Sci Rep. 2023 Mar 8;13(1):3904. doi: 10.1038/s41598-023-31067-z.

Abstract

There is still some controversy about the relationship between lipids and venous thrombosis (VTE). A bidirectional Mendelian randomization (MR) study was conducted to clarify the causal relationship between three classical lipids (low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triglycerides (TGs)) and venous thromboembolism (VTE) (deep venous thrombosis (DVT) and pulmonary embolism (PE)). Three classical lipids and VTE were analysed by bidirectional Mendelian randomization (MR). We used the random effect inverse variance weighted (IVW) model as the main analysis model and the weighted median method, simple mode method, weighted mode method and MR-Egger methods as supplementary methods. The leave-one-out test was used to determine the influence of outliers. The heterogeneity was calculated by using Cochran Q statistics in the MR-Egger and IVW methods. The intercept term in the MR‒Egger regression was used to indicate whether horizontal pleiotropy affected the results of the MR analysis. In addition, MR-PRESSO identified outlier single-nucleotide polymorphisms (SNPs) and obtained a stable result by removing outlier SNPs and then performing MR analysis. When we used three classical lipids (LDL, HDL and TGs) as exposure variables, no causal relationship between them and VTE (DVT and PE) was found. In addition, we did not find significant causal effects of VTE on the three classical lipids in reverse MR analysis. There is no significant causal relationship between three classical lipids (LDL, HDL and TGs) and VTE (DVT and PE) from a genetic point of view.

摘要

关于脂质与静脉血栓形成(VTE)之间的关系仍存在一些争议。本研究采用双向孟德尔随机化(MR)研究来阐明三种经典脂质(低密度脂蛋白(LDL)、高密度脂蛋白(HDL)和甘油三酯(TGs))与静脉血栓栓塞症(VTE)(深静脉血栓形成(DVT)和肺栓塞(PE))之间的因果关系。采用双向 MR 分析三种经典脂质与 VTE 之间的关系。我们采用随机效应逆方差加权(IVW)模型作为主要分析模型,加权中位数法、简单模式法、加权模式法和 MR-Egger 法作为补充方法。采用剔除一个观察值的方法来确定离群值的影响。在 MR-Egger 和 IVW 方法中,通过 Cochran Q 统计量来计算异质性。MR-Egger 回归中的截距项用于表示水平偏倚是否影响 MR 分析的结果。此外,MR-PRESSO 鉴定出异常单核苷酸多态性(SNPs),通过剔除异常 SNPs 并进行 MR 分析,获得了稳定的结果。当我们将三种经典脂质(LDL、HDL 和 TGs)作为暴露变量时,没有发现它们与 VTE(DVT 和 PE)之间存在因果关系。此外,在反向 MR 分析中,我们也没有发现 VTE 对三种经典脂质有显著的因果影响。从遗传角度来看,三种经典脂质(LDL、HDL 和 TGs)与 VTE(DVT 和 PE)之间没有显著的因果关系。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78b3/9995644/4bb7d771753e/41598_2023_31067_Fig1_HTML.jpg

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