Common susceptibility alleles are unlikely to contribute as strongly as the FV and ABO loci to VTE risk: results from a GWAS approach.
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.
Trégouët
David-Alexandre
DA
Inserm, Unite Mixte de Recherche S, Paris, France.
Heath
Simon
S
Saut
Noémie
N
Biron-Andreani
Christine
C
Schved
Jean-François
JF
Pernod
Gilles
G
Galan
Pilar
P
Drouet
Ludovic
L
Zelenika
Diana
D
Juhan-Vague
Irène
I
Alessi
Marie-Christine
MC
Tiret
Laurence
L
Lathrop
Mark
M
Emmerich
Joseph
J
Morange
Pierre-Emmanuel
PE
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*
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