title: Multilocus genetic risk scores for venous thromboembolism risk assessment.
abstract: BACKGROUND
  Genetics plays an important role in venous thromboembolism (VTE). Factor V Leiden (FVL or rs6025) and prothrombin gene G20210A (PT or rs1799963) are the genetic variants currently tested for VTE risk assessment. We hypothesized that primary VTE risk assessment can be improved by using genetic risk scores with more genetic markers than just FVL-rs6025 and prothrombin gene PT-rs1799963. To this end, we have designed a new genetic risk score called Thrombo inCode (TiC).
  
  
  RESULTS
  TiC was evaluated in terms of discrimination (Δ of the area under the receiver operating characteristic curve) and reclassification (integrated discrimination improvement and net reclassification improvement). This evaluation was performed using 2 age- and sex-matched case-control populations: SANTPAU (248 cases, 249 controls) and the Marseille Thrombosis Association study (MARTHA; 477 cases, 477 controls). TiC was compared with other literature-based genetic risk scores. TiC including F5 rs6025/rs118203906/rs118203905, F2 rs1799963, F12 rs1801020, F13 rs5985, SERPINC1 rs121909548, and SERPINA10 rs2232698 plus the A1 blood group (rs8176719, rs7853989, rs8176743, rs8176750) improved the area under the curve compared with a model based only on F5-rs6025 and F2-rs1799963 in SANTPAU (0.677 versus 0.575, P<0.001) and MARTHA (0.605 versus 0.576, P=0.008). TiC showed good integrated discrimination improvement of 5.49 (P<0.001) for SANTPAU and 0.96 (P=0.045) for MARTHA. Among the genetic risk scores evaluated, the proportion of VTE risk variance explained by TiC was the highest.
  
  
  CONCLUSIONS
  We conclude that TiC greatly improves prediction of VTE risk compared with other genetic risk scores. TiC should improve prevention, diagnosis, and treatment of VTE.
authors.affiliation: Unitat de Genòmica de Malalties Complexes, IIB-Sant Pau, Barcelona, Spain (J.M.S.).
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Soria
authors.affiliation: Inserm UMR_S 1062, F-13385, Aix-Marseille Université, Marseille, France (P.E.M.).
authors.forename: Pierre-Emmanuel
authors.initials: PE
authors.lastname: Morange
authors.affiliation: Grupo de Epidemiología y, Genética Cardiovascular, IMIM (Institut Hospital del Mar d'Investigacions Mèdiques), Barcelona, Spain (J.V., R.E.) CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain (J.V.).
authors.forename: Joan
authors.initials: J
authors.lastname: Vila
authors.affiliation: Unitat d'Hemostasia i Trombosis IIB-Sant Pau, Barcelona, Spain (J.C.S., J.M.).
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Souto
authors.affiliation: Gendiag.exe, Barcelona, Spain (M.M., E.S.).
authors.forename: Manel
authors.initials: M
authors.lastname: Moyano
authors.affiliation: Inserm Unité Mixte de Recherche en Santé (UMR_S) 937, ICAN Institute for Cardiometabolism and Nutrition, Université Pierre et Marie Curie Paris 6, Paris, France (D.A.T., N.S.).
authors.forename: David-Alexandre
authors.initials: DA
authors.lastname: Trégouët
authors.affiliation: Unitat d'Hemostasia i Trombosis IIB-Sant Pau, Barcelona, Spain (J.C.S., J.M.).
authors.forename: José
authors.initials: J
authors.lastname: Mateo
authors.affiliation: Inserm Unité Mixte de Recherche en Santé (UMR_S) 937, ICAN Institute for Cardiometabolism and Nutrition, Université Pierre et Marie Curie Paris 6, Paris, France (D.A.T., N.S.).
authors.forename: Noémi
authors.initials: N
authors.lastname: Saut
authors.affiliation: Gendiag.exe, Barcelona, Spain (M.M., E.S.).
authors.forename: Eduardo
authors.initials: E
authors.lastname: Salas
authors.affiliation: Grupo de Epidemiología y, Genética Cardiovascular, IMIM (Institut Hospital del Mar d'Investigacions Mèdiques), Barcelona, Spain (J.V., R.E.).
authors.forename: Roberto
authors.initials: R
authors.lastname: Elosua
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D005165:Factor V / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D005820:Genetic Testing; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D058885:Multilocus Sequence Typing; D009154:Mutation; D016017:Odds Ratio; D011237:Predictive Value of Tests; D011516:Prothrombin / Q000235:genetics*; D012044:Regression Analysis; D018570:Risk Assessment / Q000379:methods*; D013030:Spain / Q000453:epidemiology; D054556:Venous Thromboembolism / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*
chemical_list: C095381:factor V Leiden; D005165:Factor V; D011516:Prothrombin
keywords: genetics; risk factors; tests; thrombosis; veins