title: Common susceptibility alleles are unlikely to contribute as strongly as the FV and ABO loci to VTE risk: results from a GWAS approach.
abstract: 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.
authors.affiliation: Inserm, Unite Mixte de Recherche S, Paris, France.
authors.forename: David-Alexandre
authors.initials: DA
authors.lastname: Trégouët
authors.forename: Simon
authors.initials: S
authors.lastname: Heath
authors.forename: Noémie
authors.initials: N
authors.lastname: Saut
authors.forename: Christine
authors.initials: C
authors.lastname: Biron-Andreani
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Schved
authors.forename: Gilles
authors.initials: G
authors.lastname: Pernod
authors.forename: Pilar
authors.initials: P
authors.lastname: Galan
authors.forename: Ludovic
authors.initials: L
authors.lastname: Drouet
authors.forename: Diana
authors.initials: D
authors.lastname: Zelenika
authors.forename: Irène
authors.initials: I
authors.lastname: Juhan-Vague
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Alessi
authors.forename: Laurence
authors.initials: L
authors.lastname: Tiret
authors.forename: Mark
authors.initials: M
authors.lastname: Lathrop
authors.forename: Joseph
authors.initials: J
authors.lastname: Emmerich
authors.forename: Pierre-Emmanuel
authors.initials: PE
authors.lastname: Morange
mesh_terms: D000017:ABO Blood-Group System / Q000235:genetics*; D000483:Alleles; D016022:Case-Control Studies; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D000072470:Cytochrome P450 Family 4; D005165:Factor V / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D010980:Platelet Membrane Glycoproteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D054556:Venous Thromboembolism / Q000453:epidemiology / Q000235:genetics*
chemical_list: D000017:ABO Blood-Group System; D010980:Platelet Membrane Glycoproteins; C095381:factor V Leiden; C098341:platelet membrane glycoprotein VI; D005165:Factor V; D003577:Cytochrome P-450 Enzyme System; C505357:CYP4V2 protein, human; D000072470:Cytochrome P450 Family 4