title: Genetics of venous thrombosis: insights from a new genome wide association study.
abstract: BACKGROUND
  Venous Thrombosis (VT) is a common multifactorial disease associated with a major public health burden. Genetics factors are known to contribute to the susceptibility of the disease but how many genes are involved and their contribution to VT risk still remain obscure. We aimed to identify genetic variants associated with VT risk.
  
  
  RESULTS
  We conducted a genome-wide association study (GWAS) based on 551,141 SNPs genotyped in 1,542 cases and 1,110 controls. Twelve SNPs reached the genome-wide significance level of 2.0×10(-8) and encompassed four known VT-associated loci, ABO, F5, F11 and FGG. By means of haplotype analyses, we also provided novel arguments in favor of a role of HIVEP1, PROCR and STAB2, three loci recently hypothesized to participate in the susceptibility to VT. However, no novel VT-associated loci came out of our GWAS. Using a recently proposed statistical methodology, we also showed that common variants could explain about 35% of the genetic variance underlying VT susceptibility among which 3% could be attributable to the main identified VT loci. This analysis additionally suggested that the common variants left to be identified are not uniformly distributed across the genome and that chromosome 20, itself, could contribute to ∼7% of the total genetic variance.
  
  
  CONCLUSIONS
  This study might also provide a valuable source of information to expand our understanding of biological mechanisms regulating quantitative biomarkers for VT.
authors: INSERM UMR_S 937; ICAN Institute, Université Pierre et Marie Curie, Paris 6, Paris, France.
authors: Marine
authors: M
authors: Germain
authors: Noémie
authors: N
authors: Saut
authors: Nicolas
authors: N
authors: Greliche
authors: Christian
authors: C
authors: Dina
authors: Jean-Charles
authors: JC
authors: Lambert
authors: Claire
authors: C
authors: Perret
authors: William
authors: W
authors: Cohen
authors: Tiphaine
authors: T
authors: Oudot-Mellakh
authors: Guillemette
authors: G
authors: Antoni
authors: Marie-Christine
authors: MC
authors: Alessi
authors: Diana
authors: D
authors: Zelenika
authors: François
authors: F
authors: Cambien
authors: Laurence
authors: L
authors: Tiret
authors: Marion
authors: M
authors: Bertrand
authors: Anne-Marie
authors: AM
authors: Dupuy
authors: Luc
authors: L
authors: Letenneur
authors: Mark
authors: M
authors: Lathrop
authors: Joseph
authors: J
authors: Emmerich
authors: Philippe
authors: P
authors: Amouyel
authors: David-Alexandre
authors: DA
authors: Trégouët
authors: Pierre-Emmanuel
authors: PE
authors: Morange
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D019295:Computational Biology; D020022:Genetic Predisposition to Disease / Q000235:genetics; D055106:Genome-Wide Association Study / Q000379:methods*; D006239:Haplotypes; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D018401:Sample Size; D020246:Venous Thrombosis / Q000453:epidemiology / Q000235:genetics*