{"title":"静脉血栓栓塞症与缺血性中风关系的双向双样本孟德尔随机研究","authors":"Haibing Xiong, Xinhong Tian, Aiwei He, Tingting Chen, Yanlin Li, Jiajie Leng, Letai Li","doi":"10.1177/10760296241293333","DOIUrl":null,"url":null,"abstract":"<p><p>Previous clinical and epidemiological studies have shown that patients with venous thromboembolism (VTE) are comorbid with symptoms of ischaemic stroke (IS). Current understanding about increased risk of IS after VTE remain inconclusive. This study use a bidirectional two-sample Mendelian randomization (MR) study to explore the causality of VTE, pulmonary embolism (PE), deep vein thrombosis (DVT), and IS. This study used pooled data from published genome-wide association studies (GWAS). GWAS statisics of IS (from EBI database, n = 484 121), VTE (from Finngen database, n = 218 792), PE (from Finngen database, n = 218 413), and DVT (from UK biobank database, n = 337 159) were assessed. Forward and reverse MR analysis were conducted to explore the causal relationship between three type of the exposure (VTE, PE, and DVT) and the outcome (IS). Our primary causal inference method was Inverse Variance Weighted (IVW). Secondary inference methods were Weighted Median and MR-Egger. For the sensitive analysis, MR-PRESSO, MR-Egger intercept, Cochran's Q, leave-one method were used to consolidate our findings. In the foward MR analysis, VTE increased the risk of IS (OR<sub>IVW </sub>= 1.034, <i>P</i><sub>IVW </sub>= 0.021) and PE was also a risk factor for IS (OR = 1.055, <i>P</i><sub>IVW </sub>= 0.009). There was no causality that DVT influenced on IS (<i>P</i><sub>IVW </sub>> 0.05). In the reverse MR analysis, IS came to be a risk factor for DVT (OR = 1.003, <i>P</i><sub>IVW </sub>= 0.046). Meanwhile, IS took not any causal effect on VTE and PE. All the results passed the reasonable sensitive analysis. Our findings provided genetic evidence that PE and VTE can lead to an increased risk of IS, whereas increased IS promoted the risk of DVT further. Our findings provided novel insights about the risk factors and management for IS.</p>","PeriodicalId":10335,"journal":{"name":"Clinical and Applied Thrombosis/Hemostasis","volume":"30 ","pages":"10760296241293333"},"PeriodicalIF":2.3000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11528786/pdf/","citationCount":"0","resultStr":"{\"title\":\"A Bidirectional two-Sample Mendelian Randomization Study of the Association Between Venous Thromboembolism and Ischaemic Stroke.\",\"authors\":\"Haibing Xiong, Xinhong Tian, Aiwei He, Tingting Chen, Yanlin Li, Jiajie Leng, Letai Li\",\"doi\":\"10.1177/10760296241293333\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Previous clinical and epidemiological studies have shown that patients with venous thromboembolism (VTE) are comorbid with symptoms of ischaemic stroke (IS). Current understanding about increased risk of IS after VTE remain inconclusive. This study use a bidirectional two-sample Mendelian randomization (MR) study to explore the causality of VTE, pulmonary embolism (PE), deep vein thrombosis (DVT), and IS. This study used pooled data from published genome-wide association studies (GWAS). GWAS statisics of IS (from EBI database, n = 484 121), VTE (from Finngen database, n = 218 792), PE (from Finngen database, n = 218 413), and DVT (from UK biobank database, n = 337 159) were assessed. Forward and reverse MR analysis were conducted to explore the causal relationship between three type of the exposure (VTE, PE, and DVT) and the outcome (IS). Our primary causal inference method was Inverse Variance Weighted (IVW). Secondary inference methods were Weighted Median and MR-Egger. For the sensitive analysis, MR-PRESSO, MR-Egger intercept, Cochran's Q, leave-one method were used to consolidate our findings. In the foward MR analysis, VTE increased the risk of IS (OR<sub>IVW </sub>= 1.034, <i>P</i><sub>IVW </sub>= 0.021) and PE was also a risk factor for IS (OR = 1.055, <i>P</i><sub>IVW </sub>= 0.009). There was no causality that DVT influenced on IS (<i>P</i><sub>IVW </sub>> 0.05). In the reverse MR analysis, IS came to be a risk factor for DVT (OR = 1.003, <i>P</i><sub>IVW </sub>= 0.046). Meanwhile, IS took not any causal effect on VTE and PE. All the results passed the reasonable sensitive analysis. Our findings provided genetic evidence that PE and VTE can lead to an increased risk of IS, whereas increased IS promoted the risk of DVT further. 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引用次数: 0
摘要
以往的临床和流行病学研究表明,静脉血栓栓塞症(VTE)患者合并缺血性中风(IS)症状。目前关于 VTE 后 IS 风险增加的认识仍无定论。本研究采用双向双样本孟德尔随机化(MR)研究来探讨 VTE、肺栓塞(PE)、深静脉血栓形成(DVT)和 IS 的因果关系。这项研究使用了已发表的全基因组关联研究(GWAS)的汇总数据。对 IS(来自 EBI 数据库,n = 484 121)、VTE(来自 Finngen 数据库,n = 218 792)、PE(来自 Finngen 数据库,n = 218 413)和 DVT(来自英国生物库数据库,n = 337 159)的 GWAS 统计进行了评估。我们进行了正向和反向 MR 分析,以探讨三种暴露类型(VTE、PE 和 DVT)与结果(IS)之间的因果关系。我们的主要因果推断方法是反向方差加权法(IVW)。次要推断方法是加权中值法和 MR-Egger。在敏感性分析中,我们使用了 MR-PRESSO、MR-Egger 截距、Cochran's Q 和 leave-one 方法来巩固我们的研究结果。在前向 MR 分析中,VTE 增加了 IS 的风险(ORIVW = 1.034,PIVW = 0.021),PE 也是 IS 的风险因素(OR = 1.055,PIVW = 0.009)。深静脉血栓对 IS 没有影响(PIVW > 0.05)。在反向 MR 分析中,IS 成为深静脉血栓的危险因素(OR = 1.003,PIVW = 0.046)。同时,IS 对 VTE 和 PE 没有任何因果关系。所有结果都通过了合理的敏感性分析。我们的研究结果提供了遗传学证据,证明 PE 和 VTE 可导致 IS 风险的增加,而 IS 的增加会进一步增加深静脉血栓的风险。我们的研究结果为 IS 的风险因素和管理提供了新的见解。
A Bidirectional two-Sample Mendelian Randomization Study of the Association Between Venous Thromboembolism and Ischaemic Stroke.
Previous clinical and epidemiological studies have shown that patients with venous thromboembolism (VTE) are comorbid with symptoms of ischaemic stroke (IS). Current understanding about increased risk of IS after VTE remain inconclusive. This study use a bidirectional two-sample Mendelian randomization (MR) study to explore the causality of VTE, pulmonary embolism (PE), deep vein thrombosis (DVT), and IS. This study used pooled data from published genome-wide association studies (GWAS). GWAS statisics of IS (from EBI database, n = 484 121), VTE (from Finngen database, n = 218 792), PE (from Finngen database, n = 218 413), and DVT (from UK biobank database, n = 337 159) were assessed. Forward and reverse MR analysis were conducted to explore the causal relationship between three type of the exposure (VTE, PE, and DVT) and the outcome (IS). Our primary causal inference method was Inverse Variance Weighted (IVW). Secondary inference methods were Weighted Median and MR-Egger. For the sensitive analysis, MR-PRESSO, MR-Egger intercept, Cochran's Q, leave-one method were used to consolidate our findings. In the foward MR analysis, VTE increased the risk of IS (ORIVW = 1.034, PIVW = 0.021) and PE was also a risk factor for IS (OR = 1.055, PIVW = 0.009). There was no causality that DVT influenced on IS (PIVW > 0.05). In the reverse MR analysis, IS came to be a risk factor for DVT (OR = 1.003, PIVW = 0.046). Meanwhile, IS took not any causal effect on VTE and PE. All the results passed the reasonable sensitive analysis. Our findings provided genetic evidence that PE and VTE can lead to an increased risk of IS, whereas increased IS promoted the risk of DVT further. Our findings provided novel insights about the risk factors and management for IS.
期刊介绍:
CATH is a peer-reviewed bi-monthly journal that addresses the practical clinical and laboratory issues involved in managing bleeding and clotting disorders, especially those related to thrombosis, hemostasis, and vascular disorders. CATH covers clinical trials, studies on etiology, pathophysiology, diagnosis and treatment of thrombohemorrhagic disorders.