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 Blood, 21 May 2009, Vol. 113, No. 21, pp. 5298-5303.
Prepublished online as a Blood First Edition Paper on March 10, 2009; DOI 10.1182/blood-2008-11-190389.

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THROMBOSIS AND HEMOSTASIS

Common susceptibility alleles are unlikely to contribute as strongly as the FV and ABO loci to VTE risk: results from a GWAS approach

David-Alexandre Trégouët1,2, Simon Heath3, Noémie Saut4, Christine Biron-Andreani5, Jean-François Schved5, Gilles Pernod6, Pilar Galan7, Ludovic Drouet1,2, Diana Zelenika3, Irène Juhan-Vague4, Marie-Christine Alessi4, Laurence Tiret1,2, Mark Lathrop3, Joseph Emmerich8, and Pierre-Emmanuel Morange4

1 Inserm, Unite Mixte de Recherche (UMR) S937, Paris; 2 Université Pierre et Marie Curie, Université Paris 06, UMR S937, Paris; 3 Commissariat à l'Energie Atomique, Institut de Génomique, Centre National de Génotypage, Evry; 4 Inserm, UMR S626, Marseille; Université de la Méditerranée, Marseille; 5 Laboratoire d'Hématologie, Centre Hospitalier Universitaire (CHU) Montpellier, Montpellier; 6 Service de Médecine Vasculaire, CHU Grenoble, Grenoble; 7 UMR U557, Inserm U1125, Institut National de Ia Recherche Agronomique/Caisse Nationale d'Assurance Maladie Paris, Université Paris, Paris; and 8 Inserm U765, Médecine Vasculaire-Hypertension, Hôpital Européen Georges-Pompidou, Université Paris-Descartes, Paris, France

Venous thromboembolism (VTE) is a complex disease that has a major genetic component of risk. To identify genetic factors that may modify the risk of VTE, we conducted a genome-wide association study by analyzing approximately 317 000 single nucleotide polymorphisms (SNPs) in 453 VTE cases and 1327 controls. Only 3 SNPs located in the FV and ABO blood group genes were found associated with VTE at a genome-wide significant level of 1.7 x 10–7. Detailed analysis of these SNPs in additional cohorts of more than 1700 cases and 1400 controls revealed that the association observed at the FV locus was the result of the increased risk mediated by the FV Leiden mutation, whereas O and A2 blood groups were found to be at lower risk for VTE. Apart from the FV and ABO loci, no other locus was found strongly associated with VTE. However, using this large cohort of subjects, we were able to replicate the mild effects of 2 nonsynonymous SNPs, rs1613662 in GP6 and rs13146272 in CYP4V2, recently suspected to be associated with VTE.


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