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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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Submitted November 18, 2008
Accepted February 24, 2009

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

David-Alexandre Tregouet, Simon Heath, Noemie Saut, Christine Biron-Andreani, Jean-Francois Schved, Gilles Pernod, Pilar Galan, Ludovic Drouet, Diana Zelenika, Irene Juhan-Vague, Marie-Christine Alessi, Laurence Tiret, Mark Lathrop, Joseph Emmerich, and Pierre-Emmanuel Morange*

INSERM, UMR_S 937, Paris, France
Commissariat a l'Energie Atomique, Institut de Genomique, Centre National de Genotypage, Evry, France
INSERM, UMR_S 626, Universite de la Mediterranee, Marseille, France
Laboratoire d'Hematologie, CHU Montpellier, Montpellier, France
Service de Medecine Vasculaire, CHU Grenoble, Grenoble, France
UMR U557 Inserm/U1125 Inra/Cnam/Paris 13-SMBH - Universite Paris 13, Paris, France
INSERM U765, medecine vasculaire - HTA, hopital europeen Georges-Pompidou, universite Paris-Descartes, Paris, France

* Corresponding author; email: pmorange{at}ap-hm.fr.

Venous thromboembolism (VTE) is a complex disease which 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 ~317,000 single nucleotide polymorphisms (SNP) in 453 VTE cases and 1,327 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. Detail 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 due to the increased risk mediated by the FV Leiden mutation while 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 two non-synonymous SNPs, rs1613662 in GP6 and rs13146272 in CYP4V2, recently suspected to be associated with VTE.


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