03101nas a2200493 4500008004100000022001400041245016400055210006900219260001600288300001200304490000700316520162000323653001001943653002201953653000901975653002801984653004002012653001502052653001102067653003802078653001102116653000902127653001602136653003602152100002002188700002102208700002102229700001702250700002402267700001802291700002302309700002302332700001802355700002102373700001902394700001902413700002202432700003002454700002102484700001702505700002402522700002502546856003602571 2011 eng d a1460-208300aA gene-centric association scan for Coagulation Factor VII levels in European and African Americans: the Candidate Gene Association Resource (CARe) Consortium.0 agenecentric association scan for Coagulation Factor VII levels i c2011 Sep 01 a3525-340 v203 a
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.
10aAdult10aAfrican Americans10aAged10aCardiovascular Diseases10aEuropean Continental Ancestry Group10aFactor VII10aFemale10aGenetic Predisposition to Disease10aHumans10aMale10aMiddle Aged10aPolymorphism, Single Nucleotide1 aTaylor, Kira, C1 aLange, Leslie, A1 aZabaneh, Delilah1 aLange, Ethan1 aKeating, Brendan, J1 aTang, Weihong1 aSmith, Nicholas, L1 aDelaney, Joseph, A1 aKumari, Meena1 aHingorani, Aroon1 aNorth, Kari, E1 aKivimaki, Mika1 aTracy, Russell, P1 aO'Donnell, Christopher, J1 aFolsom, Aaron, R1 aGreen, David1 aHumphries, Steve, E1 aReiner, Alexander, P uhttps://chs-nhlbi.org/node/1568