|Title||Replication of a genetic risk score for venous thromboembolism in whites but not in African Americans.|
|Publication Type||Journal Article|
|Year of Publication||2016|
|Authors||Folsom AR, Tang W, Weng L-C, Roetker NS, Cushman M, Basu S|
|Secondary Authors||Pankow JS|
|Journal||J Thromb Haemost|
|Date Published||2016 Jan|
|Keywords||African Americans, Alleles, Area Under Curve, European Continental Ancestry Group, Female, Humans, Incidence, Male, Middle Aged, Polymorphism, Single Nucleotide, Proportional Hazards Models, Prospective Studies, Risk Assessment, Risk Factors, ROC Curve, United States, Venous Thromboembolism|
UNLABELLED: 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.
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.
|Alternate Journal||J Thromb Haemost|
|PubMed Central ID||PMC4715510|
|Grant List||HHSN268201100012C / HL / NHLBI NIH HHS / United States |
HHSN268201100009I / HL / NHLBI NIH HHS / United States
R01 HL103706 / HL / NHLBI NIH HHS / United States
HHSN268201100010C / HL / NHLBI NIH HHS / United States
HHSN268201100008C / HL / NHLBI NIH HHS / United States
HHSN268201100005G / HL / NHLBI NIH HHS / United States
HHSN268201100008I / HL / NHLBI NIH HHS / United States
HHSN268201100005C / / PHS HHS / United States
R01 HL059367 / HL / NHLBI NIH HHS / United States
HHSN268201100007C / HL / NHLBI NIH HHS / United States
HHSN268201100009C / / PHS HHS / United States
HHSN268201100011I / HL / NHLBI NIH HHS / United States
HHSN268201100011C / HL / NHLBI NIH HHS / United States
R01 HL59367 / HL / NHLBI NIH HHS / United States
HHSN268201100010C / / PHS HHS / United States
HHSN268201100006C / HL / NHLBI NIH HHS / United States
HHSN268201100008C / / PHS HHS / United States
HHSN268201100012C / / PHS HHS / United States
HHSN268201100005I / HL / NHLBI NIH HHS / United States
HHSN268201100007C / / PHS HHS / United States
HHSN268201100009C / HL / NHLBI NIH HHS / United States
HHSN268201100011C / / PHS HHS / United States
HHSN268201100005C / HL / NHLBI NIH HHS / United States
HHSN268201100007I / HL / NHLBI NIH HHS / United States
HHSN268201100006C / / PHS HHS / United States