Genetic risk and incident venous thromboembolism in middle-aged and older adults following COVID-19 vaccination

J Thromb Haemost. 2022 Dec;20(12):2887-2895. doi: 10.1111/jth.15879. Epub 2022 Oct 5.


Background: COVID-19 vaccination has been associated with increased venous thromboembolism (VTE) risk. However, it is unknown whether genetic predisposition to VTE is associated with an increased risk of thrombosis following vaccination.

Methods: Using data from the UK Biobank, which contains in-depth genotyping and linked vaccination and health outcomes information, we generated a polygenic risk score (PRS) using 299 genetic variants. We prospectively assessed associations between PRS and incident VTE immediately after first- and the second-dose vaccination and among historical unvaccinated cohorts during the pre- and early pandemic. We estimated hazard ratios (HR) for PRS-VTE associations using Cox models.

Results: Of 359 310 individuals receiving one dose of a COVID-19 vaccine, 160 327 (44.6%) were males, and the mean age at the vaccination date was 69.05 (standard deviation [SD] 8.04) years. After 28- and 90-days' follow-up, 88 and 299 individuals developed VTE, respectively, equivalent to an incidence rate of 0.88 (95% confidence interval [CI] 0.70-1.08) and 0.92 (0.82-1.04) per 100 000 person-days. The PRS was significantly associated with a higher risk of VTE (HR per 1 SD increase in PRS, 1.41 (1.15-1.73) in 28 days and 1.36 (1.22-1.52) in 90 days). Similar associations were found in the historical unvaccinated cohorts.

Conclusions: The strength of genetic susceptibility with post-COVID-19-vaccination VTE is similar to that seen in historical data. Additionally, the observed PRS-VTE associations were equivalent for adenovirus- and mRNA-based vaccines. These findings suggest that, at the population level, the VTE that occurred after the COVID-19 vaccination has a similar genetic etiology to the conventional VTE.

Keywords: COVID 19 vaccine; COVID-19 vaccine Pfizer-BioNTech; ChAdOx1 nCoV-19; genetic predisposition to disease; venous thromboembolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • COVID-19 Vaccines* / adverse effects
  • COVID-19* / epidemiology
  • COVID-19* / prevention & control
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Middle Aged
  • Risk Factors
  • Vaccination / adverse effects
  • Venous Thromboembolism* / epidemiology
  • Venous Thromboembolism* / etiology


  • COVID-19 Vaccines