title: Genetic variation associated with plasma von Willebrand factor levels and the risk of incident venous thrombosis.
abstract: In a recent genome-wide association study, variants in 8 genes were associated with VWF level, a risk factor for venous thrombosis (VT). In an independent, population-based, case-control study of incident VT, we tested hypotheses that variants in these genes would be associated with risk. Cases were 656 women who experienced an incident VT, and controls comprised 710 women without a history of VT. DNA was obtained from whole blood. Logistic regression was used to test associations between incident VT and single nucleotide polymorphisms (SNPs) in 7 genes not previously shown to be associated with VT. Associations with P < .05 were candidates for replication in an independent case-control study of VT in both sexes. Two of the 7 SNPs tested yielded P < .05: rs1039084 (P = .005) in STXBP5, a novel candidate gene for VT, and rs1063856 (P = .04) in VWF, a gene whose protein level is associated with VT risk. Association results for the remaining 5 variants in SCARA5, STAB2, STX2, TC2N, and CLEC4M were not significant. Both STXBP5 and VWF findings were replicated successfully. Variation in genes associated with VWF levels in the genome-wide association study was found to be independently associated with incident VT.
authors.affiliation: Department of Epidemiology, Cardiovascular Health Research Unit, University of Washington, 1730 Minor Avenue, Seattle, WA 98101, USA. nlsmith@u.washington.edu
authors.forename: Nicholas L
authors.initials: NL
authors.lastname: Smith
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Rice
authors.forename: Edwin G
authors.initials: EG
authors.lastname: Bovill
authors.forename: Mary
authors.initials: M
authors.lastname: Cushman
authors.forename: Joshua C
authors.initials: JC
authors.lastname: Bis
authors.forename: Barbara
authors.initials: B
authors.lastname: McKnight
authors.forename: Thomas
authors.initials: T
authors.lastname: Lumley
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Glazer
authors.forename: Astrid
authors.initials: A
authors.lastname: van Hylckama Vlieg
authors.forename: Weihong
authors.initials: W
authors.lastname: Tang
authors.forename: Abbas
authors.initials: A
authors.lastname: Dehghan
authors.forename: David P
authors.initials: DP
authors.lastname: Strachan
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: O'Donnell
authors.forename: Jerome I
authors.initials: JI
authors.lastname: Rotter
authors.forename: Susan R
authors.initials: SR
authors.lastname: Heckbert
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Psaty
authors.forename: Frits R
authors.initials: FR
authors.lastname: Rosendaal
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D050683:R-SNARE Proteins / Q000235:genetics*; D012307:Risk Factors; D020246:Venous Thrombosis / Q000453:epidemiology* / Q000209:etiology*; D014841:von Willebrand Factor / Q000235:genetics*
chemical_list: D009419:Nerve Tissue Proteins; D050683:R-SNARE Proteins; C484767:STXBP5 protein, human; D014841:von Willebrand Factor