Circulating adipokine concentrations and the risk of venous thromboembolism: A Mendelian randomization and mediation analysis
Background: Previous observational studies have suggested that circulating adipokine concentrations are related to a greater risk of venous thromboembolism (VTE). However, it remained unclear whether these observations reflect causality.Objective: This study aimed to investigate the causal relations...
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Frontiers Media S.A.
2023-03-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2023.1113111/full |
| _version_ | 1797859023431663616 |
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| author | Weizhong Xiao Jian Li Tianyuyi Feng Long Jin |
| author_facet | Weizhong Xiao Jian Li Tianyuyi Feng Long Jin |
| author_sort | Weizhong Xiao |
| collection | DOAJ |
| description | Background: Previous observational studies have suggested that circulating adipokine concentrations are related to a greater risk of venous thromboembolism (VTE). However, it remained unclear whether these observations reflect causality.Objective: This study aimed to investigate the causal relationship between circulating adipokine concentrations (including adiponectin, leptin, PAI-1, MCP-1, leptin receptor, and RETN) and the risk of VTE and its subtypes (DVT and PE) and to determine whether circulating adipokine concentrations are a mediator of venous thromboembolic events in obese patients.Methods: We used Mendelian randomization (MR) analyses to determine the effects of the body mass index (BMI), adiponectin, leptin, PAI-1, MCP-1, leptin receptor, and RETN levels on VTE, DVT, and PE in a cohort of 11,288 VTE cases, 5,632 DVT cases, 5,130 PE cases, and 254,771 controls. We then assessed the proportion of the effect of obesity on VTE, DVT, and PE explained by circulating leptin levels.Result: Genetically predicted higher BMI was related to increased VTE (OR = 1.45, p < 0.001), DVT (OR = 1.63, p < 0.001), and PE (OR = 1.37, p < 0.001) risk, and higher circulating leptin levels increase odds of VTE (OR = 1.96, q < 0.001), DVT (OR = 2.52, q < 0.001), and PE (OR = 2.26, q = 0.005). In addition, we found that the causal effect between elevated serum adiponectin and the decreased risk of VTE (OR = 0.85, p = 0.013, q = 0.053) and PE (OR = 0.81, p = 0.032, q = 0.083) and between MCP-1 and the reduced risk of VTE (OR = 0.88, p = 0.048, q = 0.143) is no longer significant after FDR adjustment. In MR mediation analysis, the mediation effect of circulating leptin levels in the causal pathway from BMI to PE was estimated to be 1.28 (0.95–1.71, p = 0.10), accounting for 39.14% of the total effect.Conclusion: The circulating leptin level is a risk factor for VTE, DVT, and PE, but it might be a potential mediator of BMI on the risk of PE, and thus, interventions on the circulating leptin level in obesity might reduce the risk of PE. Adiponectin is a potential protective factor for both VTE and PE. |
| first_indexed | 2024-04-09T21:22:47Z |
| format | Article |
| id | doaj.art-79bf2e266d4840b4a8ce0269f64df813 |
| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-04-09T21:22:47Z |
| publishDate | 2023-03-01 |
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| spelling | doaj.art-79bf2e266d4840b4a8ce0269f64df8132023-03-28T04:22:47ZengFrontiers Media S.A.Frontiers in Genetics1664-80212023-03-011410.3389/fgene.2023.11131111113111Circulating adipokine concentrations and the risk of venous thromboembolism: A Mendelian randomization and mediation analysisWeizhong Xiao0Jian Li1Tianyuyi Feng2Long Jin3Department of Interventional Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing, ChinaDepartment of Interventional Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing, ChinaThe Department of Radiology of the Fifth People’s Hospital of Shanghai, Fudan University, Shanghai, ChinaDepartment of Interventional Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing, ChinaBackground: Previous observational studies have suggested that circulating adipokine concentrations are related to a greater risk of venous thromboembolism (VTE). However, it remained unclear whether these observations reflect causality.Objective: This study aimed to investigate the causal relationship between circulating adipokine concentrations (including adiponectin, leptin, PAI-1, MCP-1, leptin receptor, and RETN) and the risk of VTE and its subtypes (DVT and PE) and to determine whether circulating adipokine concentrations are a mediator of venous thromboembolic events in obese patients.Methods: We used Mendelian randomization (MR) analyses to determine the effects of the body mass index (BMI), adiponectin, leptin, PAI-1, MCP-1, leptin receptor, and RETN levels on VTE, DVT, and PE in a cohort of 11,288 VTE cases, 5,632 DVT cases, 5,130 PE cases, and 254,771 controls. We then assessed the proportion of the effect of obesity on VTE, DVT, and PE explained by circulating leptin levels.Result: Genetically predicted higher BMI was related to increased VTE (OR = 1.45, p < 0.001), DVT (OR = 1.63, p < 0.001), and PE (OR = 1.37, p < 0.001) risk, and higher circulating leptin levels increase odds of VTE (OR = 1.96, q < 0.001), DVT (OR = 2.52, q < 0.001), and PE (OR = 2.26, q = 0.005). In addition, we found that the causal effect between elevated serum adiponectin and the decreased risk of VTE (OR = 0.85, p = 0.013, q = 0.053) and PE (OR = 0.81, p = 0.032, q = 0.083) and between MCP-1 and the reduced risk of VTE (OR = 0.88, p = 0.048, q = 0.143) is no longer significant after FDR adjustment. In MR mediation analysis, the mediation effect of circulating leptin levels in the causal pathway from BMI to PE was estimated to be 1.28 (0.95–1.71, p = 0.10), accounting for 39.14% of the total effect.Conclusion: The circulating leptin level is a risk factor for VTE, DVT, and PE, but it might be a potential mediator of BMI on the risk of PE, and thus, interventions on the circulating leptin level in obesity might reduce the risk of PE. Adiponectin is a potential protective factor for both VTE and PE.https://www.frontiersin.org/articles/10.3389/fgene.2023.1113111/fullMendelian randomization analysisvenous thromboembolismdeep vein thrombosispulmonary embolismadipokinemediation analysis |
| spellingShingle | Weizhong Xiao Jian Li Tianyuyi Feng Long Jin Circulating adipokine concentrations and the risk of venous thromboembolism: A Mendelian randomization and mediation analysis Frontiers in Genetics Mendelian randomization analysis venous thromboembolism deep vein thrombosis pulmonary embolism adipokine mediation analysis |
| title | Circulating adipokine concentrations and the risk of venous thromboembolism: A Mendelian randomization and mediation analysis |
| title_full | Circulating adipokine concentrations and the risk of venous thromboembolism: A Mendelian randomization and mediation analysis |
| title_fullStr | Circulating adipokine concentrations and the risk of venous thromboembolism: A Mendelian randomization and mediation analysis |
| title_full_unstemmed | Circulating adipokine concentrations and the risk of venous thromboembolism: A Mendelian randomization and mediation analysis |
| title_short | Circulating adipokine concentrations and the risk of venous thromboembolism: A Mendelian randomization and mediation analysis |
| title_sort | circulating adipokine concentrations and the risk of venous thromboembolism a mendelian randomization and mediation analysis |
| topic | Mendelian randomization analysis venous thromboembolism deep vein thrombosis pulmonary embolism adipokine mediation analysis |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2023.1113111/full |
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