Replication of a genetic risk score for venous thromboembolism in whites but not in African Americans

• Published in: Journal of thrombosis and haemostasis 2016-01, Vol.14 (1), p.83-88
• Main Authors: Folsom, A. R., Tang, W., Weng, L.‐C., Roetker, N. S., Cushman, M., Basu, S., Pankow, J. S.
• Format: Article
• Language: English
• Subjects: African Americans; Alleles; Area Under Curve; Black or African American; Confidence intervals; deep vein thrombosis; Female; genetics; Health risk assessment; Humans; Incidence; Male; Middle Aged; Polymorphism, Single Nucleotide; Proportional Hazards Models; Prospective Studies; pulmonary embolism; Risk Assessment - methods; Risk Factors; ROC Curve; Thromboembolism; United States; Venous Thromboembolism - diagnosis; Venous Thromboembolism - ethnology; Venous Thromboembolism - genetics; White People
• ISSN: 1538-7933; 1538-7836; 1538-7836
• DOI: 10.1111/jth.13193

Essentials There is little prospective information on genetic risk scores to predict venous thromboembolism (VT). Community based cohort followed a median of 22.6 years for VT occurrence. A 5‐SNP risk score identified whites at risk of VT, but not African Americans. The utility of genetic risk scores for VT is yet to be established. Summary Background Case‐control studies have created genetic risk scores of single nucleotide polymorphisms (SNPs) associated with venous thromboembolism (VTE) and documented their ability to predict VTE, but prospective data are lacking. Objective To test the ability of a genetic risk score to predict VTE incidence in a prospective study, particularly in African Americans. Methods We computed a previously proposed genetic risk score, based on five established VTE SNPs in the F5, F2, ABO, FGG, and F11 genes, in 9520 whites and 3049 African Americans initially free of VTE. We followed them a median of 22.6 years for VTE occurrence (n = 380 events in whites and n = 187 in African Americans). Results In whites, the five‐SNP weighted genetic risk score ranged from 0 to 5.8, and VTE risk increased 1.41‐fold (95% confidence interval [CI] 1.27‐fold to 1.56‐fold) per allele increment. In African Americans, the weighted genetic risk score ranged from 0 to 4.6 and the hazard ratio per risk allele was 1.14 (95% CI 0.94–1.38), with adjustment for 10 principal components of ancestry. The area under the receiver operating characteristic curve for 20‐year prediction of VTE from the weighted genetic risk score was 0.59 (95% CI 0.56–0.63) in whites and 0.56 (95% CI 0.51–0.61) in African Americans. Adding non‐genetic factors increased the area under the curve to 0.67 in whites and to 0.66 in African Americans. Conclusions Higher values for a five‐SNP genetic risk score helped identify white adults at risk of VTE. The genetic risk score did not identify future VTE occurrence in African Americans.