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Causal relationships between COVID-19 and venous thromboembolism: A mendelian randomization analysis

Hui Wang1, Sensen Wu1, Dikang Pan1

  • 1Department of Vascular Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China.

Phlebology
|July 21, 2024
PubMed

Insights

This study used Mendelian randomization to investigate a causal link between COVID-19 and venous thromboembolism (VTE). Genetic analysis found no evidence that COVID-19 causes VTE, suggesting observational links may be due to other factors.

Area of Science:

  • Genetics
  • Epidemiology
  • Internal Medicine

Background:

  • Observational studies suggest a correlation between COVID-19 and an increased risk of venous thromboembolism (VTE).
  • The causal relationship between COVID-19 and VTE remains uncertain, necessitating robust investigation.
  • Mendelian randomization (MR) offers a powerful approach to infer causality by utilizing genetic variants as instrumental variables.

Purpose of the Study:

  • To investigate the potential causal association between COVID-19 and venous thromboembolism (VTE).
  • To leverage a two-sample Mendelian randomization design to assess causality at the genetic level.
  • To differentiate genetic predisposition from environmental or confounding factors in the COVID-19-VTE association.

Main Methods:

  • Utilized a two-sample Mendelian randomization design, employing single-nucleotide polymorphisms (SNPs) associated with COVID-19 as instrumental variables (IVs).
  • Applied the inverse-variance weighted (IVW) method as the primary analysis, supplemented by weighted median, MR-Egger, and mode-based estimations.
  • Conducted sensitivity analyses including Cochran's Q test, MR-Pleiotropy Residual Sum and Outlier (MR-PRESSO), and leave-one-out analyses to ensure result robustness.

Main Results:

  • Selected instrumental variables included 26 SNPs for COVID-19 severity, 31 for hospitalization, and 13 for susceptibility.
  • Inverse-variance weighted (IVW) analysis revealed no statistically significant causal relationship between COVID-19 (severity, hospitalization, or susceptibility) and VTE.
  • Sensitivity analyses and supplementary MR methods corroborated the primary findings, indicating stable and consistent results across different analytical approaches.

Conclusions:

  • This Mendelian randomization study found no genetic evidence to support a causal link between COVID-19 and venous thromboembolism (VTE).
  • The observed associations in observational studies may be attributable to confounding factors rather than a direct causal effect of COVID-19 on VTE.
  • Further research is recommended to elucidate the mechanisms behind the association and identify potential confounding variables.

Keywords:
COVID-19mendelian randomizationvenous thromboembolism

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