title: A gene-centric association scan for Coagulation Factor VII levels in European and African Americans: the Candidate Gene Association Resource (CARe) Consortium.
abstract: Polymorphisms in several distinct genomic regions, including the F7 gene, were recently associated with factor VII (FVII) levels in European Americans (EAs). The genetic determinants of FVII in African Americans (AAs) are unknown. We used a 50,000 single nucleotide polymorphism (SNP) gene-centric array having dense coverage of over 2,000 candidate genes for cardiovascular disease (CVD) pathways in a community-based sample of 16,324 EA and 3898 AA participants from the Candidate Gene Association Resource (CARe) consortium. Our aim was the discovery of new genomic loci and more detailed characterization of existing loci associated with FVII levels. In EAs, we identified three new loci associated with FVII, of which APOA5 on chromosome 11q23 and HNF4A on chromosome 20q12-13 were replicated in a sample of 4289 participants from the Whitehall II study. We confirmed four previously reported FVII-associated loci (GCKR, MS4A6A, F7 and PROCR) in CARe EA samples. In AAs, the F7 and PROCR regions were significantly associated with FVII. Several of the FVII-associated regions are known to be associated with lipids and other cardiovascular-related traits. At the F7 locus, there was evidence of at least five independently associated SNPs in EAs and three independent signals in AAs. Though the variance in FVII explained by the existing loci is substantial (20% in EA and 10% in AA), larger sample sizes and investigation of lower frequency variants may be required to identify additional FVII-associated loci in EAs and AAs and further clarify the relationship between FVII and other CVD risk factors.
authors.affiliation: Department of Epidemiology, University of North Carolina at Chapel Hill Gillings School of Global Public Health, Chapel Hill, NC 27514, USA. kirat@email.unc.edu
authors.forename: Kira C
authors.initials: KC
authors.lastname: Taylor
authors.forename: Leslie A
authors.initials: LA
authors.lastname: Lange
authors.forename: Delilah
authors.initials: D
authors.lastname: Zabaneh
authors.forename: Ethan
authors.initials: E
authors.lastname: Lange
authors.forename: Brendan J
authors.initials: BJ
authors.lastname: Keating
authors.forename: Weihong
authors.initials: W
authors.lastname: Tang
authors.forename: Nicholas L
authors.initials: NL
authors.lastname: Smith
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Delaney
authors.forename: Meena
authors.initials: M
authors.lastname: Kumari
authors.forename: Aroon
authors.initials: A
authors.lastname: Hingorani
authors.forename: Kari E
authors.initials: KE
authors.lastname: North
authors.forename: Mika
authors.initials: M
authors.lastname: Kivimaki
authors.forename: Russell P
authors.initials: RP
authors.lastname: Tracy
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: O'Donnell
authors.forename: Aaron R
authors.initials: AR
authors.lastname: Folsom
authors.forename: David
authors.initials: D
authors.lastname: Green
authors.forename: Steve E
authors.initials: SE
authors.lastname: Humphries
authors.forename: Alexander P
authors.initials: AP
authors.lastname: Reiner
mesh_terms: D000328:Adult; D001741:Black or African American; D000368:Aged; D002318:Cardiovascular Diseases / Q000097:blood / Q000235:genetics; D005167:Factor VII / Q000378:metabolism*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D044465:White People
chemical_list: D005167:Factor VII