Multilocus genetic risk scores for venous thromboembolism risk assessment
Soria Fernández, José Manuel (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Morange, Pierre-Emmanuel (Aix-Marseille Université)
Vila, Joan (Institut Hospital del Mar d'Investigacions Mèdiques)
Souto, Juan Carlos (Institut d'Investigació Biomèdica Sant Pau)
Moyano, Manel (Gendiag.exe (Barcelona))
Trégouët, David-Alexandre (Université Pierre et Marie Curie)
Mateo, José (Institut d'Investigació Biomèdica Sant Pau)
Saut, Noémi (Université Pierre et Marie Curie)
Salas, Eduardo (Gendiag.exe (Barcelona))
Elosua, Roberto (Institut Hospital del Mar d'Investigacions Mèdiques)
Universitat Autònoma de Barcelona

Date:	2014
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). Methods and 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.
Grants:	Ministerio de Economía y Competitividad RD12/0042/0032 Ministerio de Economía y Competitividad RD12/0042/0061 Ministerio de Economía y Competitividad FI12/00322
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Genetics ; Risk factors ; Tests ; Thrombosis ; Veins
Published in:	Journal of the American Heart Association. Cardiovascular and cerebrovascular disease, Vol. 3 Núm. 5 (2014) , p. e001060, ISSN 2047-9980

DOI: 10.1161/JAHA.114.001060
PMID: 25341889

10 p, 303.8 KB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
Articles > Published articles