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Circulating Cytokines and Venous Thromboembolism: A Bidirectional Two-Sample Mendelian Randomization Study.

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This study used genetic data to investigate the causal link between circulating cytokines and venous thromboembolism (VTE). Findings suggest a bidirectional relationship, indicating potential therapeutic targets for VTE prevention.

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Area of Science:

  • Genetics and Molecular Biology
  • Cardiovascular Medicine
  • Immunology

Background:

  • Epidemiological studies suggest a link between circulating cytokines and venous thromboembolism (VTE).
  • The causal nature of this association remains unclear due to potential confounding factors and reverse causality.
  • This study investigates the causal relationship between cytokines and VTE, including deep vein thrombosis (DVT) and pulmonary embolism (PE).

Purpose of the Study:

  • To explore the bidirectional causal effects between circulating cytokines and VTE using a Mendelian randomization approach.
  • To identify specific cytokines causally associated with VTE risk.
  • To investigate potential mediating factors and reverse causality between VTE and cytokine levels.

Main Methods:

  • A bidirectional Mendelian randomization (MR) study design was employed.
  • Instrumental variables for 41 circulating cytokines were derived from genome-wide association study meta-analyses.
  • Summary statistics for VTE, DVT, and PE were obtained from the FinnGen Study, with multivariable MR used for confounder adjustment.

Main Results:

  • Stromal cell-derived factor-1α showed a suggestive inverse association with VTE and DVT risk.
  • Granulocyte colony-stimulating factor was suggestively associated with an increased risk of PE.
  • Multivariable MR indicated that hemoglobin A1c and systolic blood pressure partially mediate the effect of cytokines on VTE; reverse MR suggested VTE influences cytokine levels.

Conclusions:

  • Suggestive genetic evidence supports a bidirectional causal relationship between circulating cytokines and VTE.
  • Targeting specific circulating cytokines may offer a novel strategy for reducing VTE incidence.
  • Further research is warranted to elucidate the complex interplay between cytokines and thromboembolic events.