Wei Huang, Yan Zou, Kun Zhang, Shi Yao, Shi-Hao Tang, Hao Wu, Peng-Fei Wang, Han-Zhong Xue, Tie-Lin Yang, Kun Zhang, Yan Guo
{"title":"双样本孟德尔随机分析揭示了血脂与静脉血栓栓塞之间的因果关系。","authors":"Wei Huang, Yan Zou, Kun Zhang, Shi Yao, Shi-Hao Tang, Hao Wu, Peng-Fei Wang, Han-Zhong Xue, Tie-Lin Yang, Kun Zhang, Yan Guo","doi":"10.3324/haematol.2023.284566","DOIUrl":null,"url":null,"abstract":"<p><p>Venous thromboembolism (VTE) is a complex disease that can be classified into two subtypes: deep vein thrombosis (DVT) and pulmonary embolism (PE). Previous observational studies have shown associations between lipids and VTE, but causality remains unclear. Hence, by utilizing 241 lipid-related traits as exposures and data from the FinnGen consortium on VTE, DVT, and PE as outcomes, we conducted two-sample Mendelian randomization (MR) analysis to investigate causal relationships between lipids and VTE, DVT and PE. The MR results identified that fatty acid (FA) unsaturation traits (ratio of bis-allylic bonds to double bonds in lipids, and ratio of bis-allylic bonds to total fatty acids in lipids) were associated with VTE (odds ratio [OR]=1.21, 95% confidence interval [CI]: 1.15-1.27; OR=1.21, 95% CI: 1.13-1.30), DVT (OR=1.24, 95% CI: 1.16-1.33; OR= 1.26, 95% CI: 1.16-1.36) and PE (OR=1.18, 95% CI: 1.08-1.29; OR=1.18, 95% CI: 1.09-1.27). Phosphatidylcholines (PC) exhibit potential causal effects on VTE and PE. PC acyl-alkyl C40:4 (PC ae C40:4) was negatively associated with VTE (OR=0.79, 95% CI: 0.73-0.86), while PC diacyl C42:6 (PC aa C42:6) and PC acyl-alkyl C36:4 (PC ae C36:4) were positively associated with PE (OR=1.44, 95% CI: 1.20-1.72; OR=1.22, 95% CI: 1.10-1.35). Additionally, we found that medium LDL had a protective effect on VTE. Our study indicates that higher FA unsaturation may increase the risk of VTE, DVT, and PE. Different types of PC have either promotive or inhibitory effects on VTE and PE, contributing to a better understanding of the risk factors for VTE.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":null,"pages":null},"PeriodicalIF":8.2000,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11367238/pdf/","citationCount":"0","resultStr":"{\"title\":\"Two-sample Mendelian randomization analysis reveals causal relationships between blood lipids and venous thromboembolism.\",\"authors\":\"Wei Huang, Yan Zou, Kun Zhang, Shi Yao, Shi-Hao Tang, Hao Wu, Peng-Fei Wang, Han-Zhong Xue, Tie-Lin Yang, Kun Zhang, Yan Guo\",\"doi\":\"10.3324/haematol.2023.284566\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Venous thromboembolism (VTE) is a complex disease that can be classified into two subtypes: deep vein thrombosis (DVT) and pulmonary embolism (PE). Previous observational studies have shown associations between lipids and VTE, but causality remains unclear. Hence, by utilizing 241 lipid-related traits as exposures and data from the FinnGen consortium on VTE, DVT, and PE as outcomes, we conducted two-sample Mendelian randomization (MR) analysis to investigate causal relationships between lipids and VTE, DVT and PE. The MR results identified that fatty acid (FA) unsaturation traits (ratio of bis-allylic bonds to double bonds in lipids, and ratio of bis-allylic bonds to total fatty acids in lipids) were associated with VTE (odds ratio [OR]=1.21, 95% confidence interval [CI]: 1.15-1.27; OR=1.21, 95% CI: 1.13-1.30), DVT (OR=1.24, 95% CI: 1.16-1.33; OR= 1.26, 95% CI: 1.16-1.36) and PE (OR=1.18, 95% CI: 1.08-1.29; OR=1.18, 95% CI: 1.09-1.27). Phosphatidylcholines (PC) exhibit potential causal effects on VTE and PE. PC acyl-alkyl C40:4 (PC ae C40:4) was negatively associated with VTE (OR=0.79, 95% CI: 0.73-0.86), while PC diacyl C42:6 (PC aa C42:6) and PC acyl-alkyl C36:4 (PC ae C36:4) were positively associated with PE (OR=1.44, 95% CI: 1.20-1.72; OR=1.22, 95% CI: 1.10-1.35). Additionally, we found that medium LDL had a protective effect on VTE. Our study indicates that higher FA unsaturation may increase the risk of VTE, DVT, and PE. Different types of PC have either promotive or inhibitory effects on VTE and PE, contributing to a better understanding of the risk factors for VTE.</p>\",\"PeriodicalId\":12964,\"journal\":{\"name\":\"Haematologica\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":8.2000,\"publicationDate\":\"2024-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11367238/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Haematologica\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.3324/haematol.2023.284566\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"HEMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Haematologica","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3324/haematol.2023.284566","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"HEMATOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
静脉血栓栓塞症(VTE)是一种复杂的疾病,可分为两种亚型:深静脉血栓(DVT)和肺栓塞(PE)。以往的观察性研究显示血脂与 VTE 之间存在关联,但因果关系仍不明确。因此,我们利用 241 个血脂相关特征作为暴露因子,并利用 FinnGen 联合研究小组关于 VTE、DVT 和 PE 的数据作为结果,进行了双样本孟德尔随机化(MR)分析,以研究血脂与 VTE、DVT 和 PE 之间的因果关系。MR 结果表明,脂肪酸(FA)不饱和性状(脂质中双烯丙基键与双键之比、脂质中双烯丙基键与总脂肪酸之比)与 VTE 相关(OR [95% CI]: 1.21[1.15-1.27];1.21[1.13-1.30])、深静脉血栓(OR [95%CI]:1.24 [1.16-1.33];1.26 [1.16-1.36])和 PE(OR [95%CI]:1.18 [1.08-1.29];1.18 [1.09-1.27])相关。磷脂酰胆碱对 VTE 和 PE 具有潜在的因果效应。磷脂酰胆碱酰基烷基 C40:4(PC ae C40:4)与 VTE 呈负相关(OR [95% CI]:0.79 [0.73-0.86]),而磷脂酰胆碱二酰基 C42:6(PC aa C42:6)和磷脂酰胆碱酰基烷基 C36:4(PC ae C36:4)与 PE 呈正相关(OR [95%CI]:1.44 [1.20-1.72];1.22 [1.10-1.35])。此外,我们还发现中等低密度脂蛋白对 VTE 有保护作用。我们的研究表明,较高的 FA 不饱和度可能会增加 VTE、DVT 和 PE 的风险。不同类型的磷脂酰胆碱对 VTE 和 PE 有促进或抑制作用,有助于更好地了解 VTE 的风险因素。
Two-sample Mendelian randomization analysis reveals causal relationships between blood lipids and venous thromboembolism.
Venous thromboembolism (VTE) is a complex disease that can be classified into two subtypes: deep vein thrombosis (DVT) and pulmonary embolism (PE). Previous observational studies have shown associations between lipids and VTE, but causality remains unclear. Hence, by utilizing 241 lipid-related traits as exposures and data from the FinnGen consortium on VTE, DVT, and PE as outcomes, we conducted two-sample Mendelian randomization (MR) analysis to investigate causal relationships between lipids and VTE, DVT and PE. The MR results identified that fatty acid (FA) unsaturation traits (ratio of bis-allylic bonds to double bonds in lipids, and ratio of bis-allylic bonds to total fatty acids in lipids) were associated with VTE (odds ratio [OR]=1.21, 95% confidence interval [CI]: 1.15-1.27; OR=1.21, 95% CI: 1.13-1.30), DVT (OR=1.24, 95% CI: 1.16-1.33; OR= 1.26, 95% CI: 1.16-1.36) and PE (OR=1.18, 95% CI: 1.08-1.29; OR=1.18, 95% CI: 1.09-1.27). Phosphatidylcholines (PC) exhibit potential causal effects on VTE and PE. PC acyl-alkyl C40:4 (PC ae C40:4) was negatively associated with VTE (OR=0.79, 95% CI: 0.73-0.86), while PC diacyl C42:6 (PC aa C42:6) and PC acyl-alkyl C36:4 (PC ae C36:4) were positively associated with PE (OR=1.44, 95% CI: 1.20-1.72; OR=1.22, 95% CI: 1.10-1.35). Additionally, we found that medium LDL had a protective effect on VTE. Our study indicates that higher FA unsaturation may increase the risk of VTE, DVT, and PE. Different types of PC have either promotive or inhibitory effects on VTE and PE, contributing to a better understanding of the risk factors for VTE.
期刊介绍:
Haematologica is a journal that publishes articles within the broad field of hematology. It reports on novel findings in basic, clinical, and translational research.
Scope:
The scope of the journal includes reporting novel research results that:
Have a significant impact on understanding normal hematology or the development of hematological diseases.
Are likely to bring important changes to the diagnosis or treatment of hematological diseases.