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

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.