Bidirectional two-sample Mendelian randomization analysis identifies protein C rather than protein S or antithrombin-III as associated with deep venous thrombosis
Introduction Observational studies have indicated significant contributions of protein C and protein S to thrombotic diseases, yet the “anticoagulation paradox” in deep venous thrombosis (DVT) remains unresolved. Therefore, we conducted an investigation to discern the causal effects of protein C, pr...
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Termedia Publishing House
2024-06-01
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| Series: | Archives of Medical Science |
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| Online Access: | https://www.archivesofmedicalscience.com/Bidirectional-two-sample-Mendelian-randomization-analysis-identifies-protein-C-rather,188205,0,2.html |
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| author | Liang Shu Liyan Sun Cong Yu Dabin Ren Yisong Zhang Ping Zheng |
| author_facet | Liang Shu Liyan Sun Cong Yu Dabin Ren Yisong Zhang Ping Zheng |
| author_sort | Liang Shu |
| collection | DOAJ |
| description | Introduction
Observational studies have indicated significant contributions of protein C and protein S to thrombotic diseases, yet the “anticoagulation paradox” in deep venous thrombosis (DVT) remains unresolved. Therefore, we conducted an investigation to discern the causal effects of protein C, protein S and antithrombin-III on DVT risk.
Material and methods
We employed a two-sample (one to evaluate the gene-exposure relationship and the other to evaluate the gene-outcome relationship) bidirectional Mendelian randomization (MR) framework to assess the causal associations between protein C, protein S, antithrombin-III and DVT.
Results
Genetic associations with DVT were extracted from a comprehensive genome-wide association study involving 484,598 individuals. In the multivariable MR analysis, the odds ratios for DVT per standard deviation (SD) increase were 1.005 (95% CI: 1.002–1.008; p < 0.001) for protein C, 0.997 (95% CI: 0.992–1.001; p = 0.146) for protein S, and 1.001 (95% CI: 0.998–1.005; p = 0.456) for antithrombin-III. A two-step MR mediation analysis revealed that the association between protein C and DVT was partially mediated by body mass index, with a mediated proportion of 11.4% (95% confidence interval, 2.3% to 79.2%).
Conclusions
These findings provide insights into the genetic relationship between relative protein C rather than protein S or antithrombin-III levels and DVT, offering potential utility in identifying at-risk patients for DVT development. |
| format | Article |
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| institution | OA Journals |
| issn | 1734-1922 1896-9151 |
| language | English |
| publishDate | 2024-06-01 |
| publisher | Termedia Publishing House |
| record_format | Article |
| series | Archives of Medical Science |
| spelling | doaj-art-935bd1cc16de42b087ef73bd26c31a4c2025-08-20T02:31:34ZengTermedia Publishing HouseArchives of Medical Science1734-19221896-91512024-06-0121121522310.5114/aoms/188205188205Bidirectional two-sample Mendelian randomization analysis identifies protein C rather than protein S or antithrombin-III as associated with deep venous thrombosisLiang Shu0Liyan Sun1Cong Yu2Dabin Ren3Yisong Zhang4Ping Zheng5Department of Neurology, Shanghai Ninth People’s Hospital, Shanghai, ChinaDepartment of Obstetrics and Gynecology, Shanghai Pudong New area People’s Hospital, Shanghai, ChinaDepartment of Neurosurgery, Shanghai Pudong New area People’s Hospital, Shanghai, ChinaDepartment of Neurosurgery, Shanghai Pudong New area People’s Hospital, Shanghai, ChinaDepartment of Neurosurgery, Shanghai Pudong New area People’s Hospital, Shanghai, ChinaDepartment of Neurosurgery, Shanghai Pudong New area People’s Hospital, Shanghai, ChinaIntroduction Observational studies have indicated significant contributions of protein C and protein S to thrombotic diseases, yet the “anticoagulation paradox” in deep venous thrombosis (DVT) remains unresolved. Therefore, we conducted an investigation to discern the causal effects of protein C, protein S and antithrombin-III on DVT risk. Material and methods We employed a two-sample (one to evaluate the gene-exposure relationship and the other to evaluate the gene-outcome relationship) bidirectional Mendelian randomization (MR) framework to assess the causal associations between protein C, protein S, antithrombin-III and DVT. Results Genetic associations with DVT were extracted from a comprehensive genome-wide association study involving 484,598 individuals. In the multivariable MR analysis, the odds ratios for DVT per standard deviation (SD) increase were 1.005 (95% CI: 1.002–1.008; p < 0.001) for protein C, 0.997 (95% CI: 0.992–1.001; p = 0.146) for protein S, and 1.001 (95% CI: 0.998–1.005; p = 0.456) for antithrombin-III. A two-step MR mediation analysis revealed that the association between protein C and DVT was partially mediated by body mass index, with a mediated proportion of 11.4% (95% confidence interval, 2.3% to 79.2%). Conclusions These findings provide insights into the genetic relationship between relative protein C rather than protein S or antithrombin-III levels and DVT, offering potential utility in identifying at-risk patients for DVT development.https://www.archivesofmedicalscience.com/Bidirectional-two-sample-Mendelian-randomization-analysis-identifies-protein-C-rather,188205,0,2.htmlprotein cdeep venous thrombosiscausal effectmendelian randomizationmediating effect |
| spellingShingle | Liang Shu Liyan Sun Cong Yu Dabin Ren Yisong Zhang Ping Zheng Bidirectional two-sample Mendelian randomization analysis identifies protein C rather than protein S or antithrombin-III as associated with deep venous thrombosis Archives of Medical Science protein c deep venous thrombosis causal effect mendelian randomization mediating effect |
| title | Bidirectional two-sample Mendelian randomization analysis identifies protein C rather than protein S or antithrombin-III as associated with deep venous thrombosis |
| title_full | Bidirectional two-sample Mendelian randomization analysis identifies protein C rather than protein S or antithrombin-III as associated with deep venous thrombosis |
| title_fullStr | Bidirectional two-sample Mendelian randomization analysis identifies protein C rather than protein S or antithrombin-III as associated with deep venous thrombosis |
| title_full_unstemmed | Bidirectional two-sample Mendelian randomization analysis identifies protein C rather than protein S or antithrombin-III as associated with deep venous thrombosis |
| title_short | Bidirectional two-sample Mendelian randomization analysis identifies protein C rather than protein S or antithrombin-III as associated with deep venous thrombosis |
| title_sort | bidirectional two sample mendelian randomization analysis identifies protein c rather than protein s or antithrombin iii as associated with deep venous thrombosis |
| topic | protein c deep venous thrombosis causal effect mendelian randomization mediating effect |
| url | https://www.archivesofmedicalscience.com/Bidirectional-two-sample-Mendelian-randomization-analysis-identifies-protein-C-rather,188205,0,2.html |
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