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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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Termedia Publishing House
2024-06-01
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| Series: | Archives of Medical Science |
| Subjects: | |
| Online Access: | https://www.archivesofmedicalscience.com/Bidirectional-two-sample-Mendelian-randomization-analysis-identifies-protein-C-rather,188205,0,2.html |
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| Summary: | 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. |
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| ISSN: | 1734-1922 1896-9151 |