Title | Prediction of primary venous thromboembolism based on clinical and genetic factors within the U.K. Biobank. |
Publication Type | Journal Article |
Year of Publication | 2021 |
Authors | Kolin DA, Kulm S, Elemento O |
Journal | Sci Rep |
Volume | 11 |
Issue | 1 |
Pagination | 21340 |
Date Published | 2021 Nov 01 |
ISSN | 2045-2322 |
Keywords | Adult, Aged, Female, Genetic Predisposition to Disease, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Prognosis, Proportional Hazards Models, Prospective Studies, Risk Factors, United Kingdom, Venous Thromboembolism |
Abstract | Both clinical and genetic factors drive the risk of venous thromboembolism. However, whether clinically recorded risk factors and genetic variants can be combined into a clinically applicable predictive score remains unknown. Using Cox proportional-hazard models, we analyzed the association of risk factors with the likelihood of venous thromboembolism in U.K. Biobank, a large prospective cohort. We then created a polygenic risk score of 36 single nucleotide polymorphisms and a clinical score determined by age, sex, body mass index, previous cancer diagnosis, smoking status, and fracture in the last 5 years. Participants were at significantly increased risk of venous thromboembolism if they were at high clinical risk (subhazard ratio, 4.37 [95% CI, 3.85-4.97]) or high genetic risk (subhazard ratio, 3.02 [95% CI, 2.63-3.47]) relative to participants at low clinical or genetic risk, respectively. The combined model, consisting of clinical and genetic components, was significantly better than either the clinical or the genetic model alone (P < 0.001). Participants at high risk in the combined score had nearly an eightfold increased risk of venous thromboembolism relative to participants at low risk (subhazard ratio, 7.51 [95% CI, 6.28-8.98]). This risk score can be used to guide decisions regarding venous thromboembolism prophylaxis, although external validation is needed. |
DOI | 10.1038/s41598-021-00796-4 |
Alternate Journal | Sci Rep |
PubMed ID | 34725413 |
PubMed Central ID | PMC8560817 |
Grant List | MC_PC_17228 / MRC_ / Medical Research Council / United Kingdom U24 CA210989 / NH / NIH HHS / United States U24 CA210989 / CA / NCI NIH HHS / United States P50 CA211024 / CA / NCI NIH HHS / United States R01 CA194547 / CA / NCI NIH HHS / United States MC_QA137853 / MRC_ / Medical Research Council / United Kingdom |