title: Genetic variants associated with Von Willebrand factor levels in healthy men and women identified using the HumanCVD BeadChip.
abstract: We have used the gene-centric Illumina HumanCVD BeadChip to identify common genetic determinants of Von Willebrand factor (vWF) levels in healthy men and women. The Whitehall II (WHII) study (n= 5592) and the British Women's Heart and Health Study (BWHHS) (n= 3445) were genotyped using the HumanCVD BeadChip. Replication was conducted in the British Regional Heart Study (n= 3897) and 1958 Birth Cohort (n= 5048). We identified 48 single nucleotide polymorphisms (SNPs) in four genes/regions associated with vWF at P < 10(-4) . These included 19 SNPs at the ABO blood group locus with the lead variant being rs657152 (P= 9.7 × 10(-233) ). The lead variant in the 24 VWF SNPs was rs1063856 (P= 2.3 × 10(-20) ). SNPs at ESR1 (rs6909023) and NRG1(rs1685103) showed modest associations with vWF, but these were not confirmed in a meta-analysis. Using variable selection, five SNPs at the locus for ABO and two for VWF were found to have independent associations with vWF levels. After adjustment for age and gender, the selected ABO SNPs explained 15% and the VWF SNPs an additional 2% of the variance in vWF levels. Individuals at opposite tails of the additive seven SNP allele score exhibited substantial differences in vWF levels. These data demonstrate that multiple common alleles with small effects make, in combination, important contributions to individual differences in vWF levels.
authors.affiliation: University College London Genetics Institute, Department of Genetics, Environment and Evolution, London, UK.
authors.forename: Delilah
authors.initials: D
authors.lastname: Zabaneh
authors.forename: Tom R
authors.initials: TR
authors.lastname: Gaunt
authors.forename: Meena
authors.initials: M
authors.lastname: Kumari
authors.forename: Fotios
authors.initials: F
authors.lastname: Drenos
authors.forename: Sonia
authors.initials: S
authors.lastname: Shah
authors.forename: Diane
authors.initials: D
authors.lastname: Berry
authors.forename: Chris
authors.initials: C
authors.lastname: Power
authors.forename: Elina
authors.initials: E
authors.lastname: Hypponen
authors.forename: Tina
authors.initials: T
authors.lastname: Shah
authors.forename: Jutta
authors.initials: J
authors.lastname: Palmen
authors.forename: Jacky
authors.initials: J
authors.lastname: Pallas
authors.forename: Philippa J
authors.initials: PJ
authors.lastname: Talmud
authors.forename: Juan Pablo
authors.initials: JP
authors.lastname: Casas
authors.forename: Reecha
authors.initials: R
authors.lastname: Sofat
authors.forename: Gordon
authors.initials: G
authors.lastname: Lowe
authors.forename: Ann
authors.initials: A
authors.lastname: Rumley
authors.forename: Richard W
authors.initials: RW
authors.lastname: Morris
authors.forename: Peter H
authors.initials: PH
authors.lastname: Whincup
authors.forename: Santiago
authors.initials: S
authors.lastname: Rodriguez
authors.forename: Shah
authors.initials: S
authors.lastname: Ebrahim
authors.forename: Michael G
authors.initials: MG
authors.lastname: Marmot
authors.forename: George Davey
authors.initials: GD
authors.lastname: Smith
authors.forename: Debbie A
authors.initials: DA
authors.lastname: Lawlor
authors.forename: Mika
authors.initials: M
authors.lastname: Kivimaki
authors.forename: John
authors.initials: J
authors.lastname: Whittaker
authors.forename: Aroon D
authors.initials: AD
authors.lastname: Hingorani
authors.forename: Ian N
authors.initials: IN
authors.lastname: Day
authors.forename: Steve E
authors.initials: SE
authors.lastname: Humphries
mesh_terms: D000017:ABO Blood-Group System / Q000235:genetics; D005260:Female; D005821:Genetic Techniques; D005838:Genotype; D006801:Humans; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011159:Population Surveillance; D014841:von Willebrand Factor / Q000235:genetics*
chemical_list: D000017:ABO Blood-Group System; D014841:von Willebrand Factor