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

• Published in: Scientific reports Vol. 11; no. 1; p. 21340
• Main Authors: Kolin, David A., Kulm, Scott, Elemento, Olivier
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-11-2021; Nature Publishing Group; Nature Portfolio
• Subjects: 631/208; 692/308/174; 692/308/2056; 692/499; Adult; Aged; Biobanks; Body mass index; Female; Genetic diversity; Genetic factors; Genetic Predisposition to Disease; Genetic variance; Humanities and Social Sciences; Humans; Male; Middle Aged; multidisciplinary; Polymorphism, Single Nucleotide; Prognosis; Prophylaxis; Proportional Hazards Models; Prospective Studies; Risk Factors; Science; Science (multidisciplinary); Single-nucleotide polymorphism; Thromboembolism; United Kingdom - epidemiology; Venous Thromboembolism - diagnosis; Venous Thromboembolism - etiology; Venous Thromboembolism - genetics; United Kingdom; United Kingdom > UK
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-00796-4

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.