title: Replication of a genetic risk score for venous thromboembolism in whites but not in African Americans.
abstract: 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.
authors.affiliation: Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA.
authors.forename: A R
authors.initials: AR
authors.lastname: Folsom
authors.affiliation: Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA.
authors.forename: W
authors.initials: W
authors.lastname: Tang
authors.affiliation: Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA.
authors.forename: L-C
authors.initials: LC
authors.lastname: Weng
authors.affiliation: Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA.
authors.forename: N S
authors.initials: NS
authors.lastname: Roetker
authors.affiliation: Department of Medicine, University of Vermont, Burlington, VT, USA.|Department of Pathology, University of Vermont, Burlington, VT, USA.
authors.forename: M
authors.initials: M
authors.lastname: Cushman
authors.affiliation: Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN, USA.
authors.forename: S
authors.initials: S
authors.lastname: Basu
authors.affiliation: Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA.
authors.forename: J S
authors.initials: JS
authors.lastname: Pankow
mesh_terms: D001741:Black or African American; D000483:Alleles; D019540:Area Under Curve; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012372:ROC Curve; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors; D014481:United States; D054556:Venous Thromboembolism / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D044465:White People
keywords: deep vein thrombosis; genetics; prospective studies; pulmonary embolism; risk factors