Englander Institute for Precision Medicine

Prediction of primary venous thromboembolism based on clinical and genetic factors within the U.K. Biobank.

TitlePrediction of primary venous thromboembolism based on clinical and genetic factors within the U.K. Biobank.
Publication TypeJournal Article
Year of Publication2021
AuthorsKolin DA, Kulm S, Elemento O
JournalSci Rep
Volume11
Issue1
Pagination21340
Date Published2021 Nov 01
ISSN2045-2322
KeywordsAdult, 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.

DOI10.1038/s41598-021-00796-4
Alternate JournalSci Rep
PubMed ID34725413
PubMed Central IDPMC8560817
Grant ListMC_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

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