Genetic risk and incident venous thromboembolism in middle-aged and older adults following COVID-19 vaccination.
Xie J., Prats-Uribe A., Gordillo-Marañón M., Strauss VY., Gill D., Prieto-Alhambra D.
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 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 to 1.08) and 0.92 (0.82 to 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 to 1.73) in 28 days and 1.36 (1.22 to 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 aetiology to the conventional VTE.