title: A genome-wide search for common SNP x SNP interactions on the risk of venous thrombosis.
abstract: BACKGROUND
  Venous Thrombosis (VT) is a common multifactorial disease with an estimated heritability between 35% and 60%. Known genetic polymorphisms identified so far only explain ~5% of the genetic variance of the disease. This study was aimed to investigate whether pair-wise interactions between common single nucleotide polymorphisms (SNPs) could exist and modulate the risk of VT.
  
  
  METHODS
  A genome-wide SNP x SNP interaction analysis on VT risk was conducted in a French case-control study and the most significant findings were tested for replication in a second independent French case-control sample. The results obtained in the two studies totaling 1,953 cases and 2,338 healthy subjects were combined into a meta-analysis.
  
  
  RESULTS
  The smallest observed p-value for interaction was p = 6.00 10(-11) but it did not pass the Bonferroni significance threshold of 1.69 10(-12) correcting for the number of investigated interactions that was 2.96 10(10). Among the 37 suggestive pair-wise interactions with p-value less than 10(-8), one was further shown to involve two SNPs, rs9804128 (IGFS21 locus) and rs4784379 (IRX3 locus) that demonstrated significant interactive effects (p = 4.83 10(-5)) on the variability of plasma Factor VIII levels, a quantitative biomarker of VT risk, in a sample of 1,091 VT patients.
  
  
  CONCLUSIONS
  This study, the first genome-wide SNP interaction analysis conducted so far on VT risk, suggests that common SNPs are unlikely exerting strong interactive effects on the risk of disease.
authors.affiliation: INSERM, UMR_S 937; Institute of Cardiometabolism And Nutrition (ICAN), Université Pierre et Marie Curie Paris 6, Paris F-75013, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Greliche
authors.forename: Marine
authors.initials: M
authors.lastname: Germain
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Lambert
authors.forename: William
authors.initials: W
authors.lastname: Cohen
authors.forename: Marion
authors.initials: M
authors.lastname: Bertrand
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Dupuis
authors.forename: Luc
authors.initials: L
authors.lastname: Letenneur
authors.forename: Mark
authors.initials: M
authors.lastname: Lathrop
authors.forename: Philippe
authors.initials: P
authors.lastname: Amouyel
authors.forename: Pierre-Emmanuel
authors.initials: PE
authors.lastname: Morange
authors.forename: David-Alexandre
authors.initials: DA
authors.lastname: Trégouët
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D004843:Epistasis, Genetic; D005169:Factor VIII / Q000235:genetics / Q000378:metabolism; D005260:Female; D005602:France; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D014157:Transcription Factors / Q000235:genetics; D020246:Venous Thrombosis / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: D018398:Homeodomain Proteins; C501598:IRX3 protein, human; D014157:Transcription Factors; D005169:Factor VIII