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A gene-centric association scan for Coagulation Factor VII levels in European and African Americans: the Candidate Gene Association Resource (CARe) Consortium.
Tuesday,2013-01-15 11:11 America/Los_Angeles — poolea2
| Title | A gene-centric association scan for Coagulation Factor VII levels in European and African Americans: the Candidate Gene Association Resource (CARe) Consortium. |
| Publication Type | Journal Article |
| Year of Publication | 2011 |
| Authors | Taylor, KC, Lange, LA, Zabaneh, D, Lange, E, Keating, BJ, Tang, W, Smith, NL, Delaney, JA, Kumari, M, Hingorani, A, North, KE, Kivimaki, M, Tracy, RP, O'Donnell, CJ, Folsom, AR, Green, D, Humphries, SE, Reiner, AP |
| Journal | Hum Mol Genet |
| Volume | 20 |
| Issue | 17 |
| Pagination | 3525-34 |
| Date Published | 2011 Sep 01 |
| ISSN | 1460-2083 |
| Keywords | Adult, African Americans, Aged, Cardiovascular Diseases, European Continental Ancestry Group, Factor VII, Female, Genetic Predisposition to Disease, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide |
| Abstract | <p>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.</p> |
| DOI | 10.1093/hmg/ddr264 |
| Alternate Journal | Hum. Mol. Genet. |
| PubMed ID | 21676895 |
| PubMed Central ID | PMC3153310 |
| Grant List | 5T32HL007055-34 / HL / NHLBI NIH HHS / United States / / British Heart Foundation / United Kingdom RG/08/008/25291 / / British Heart Foundation / United Kingdom G19/35 / / Medical Research Council / United Kingdom G0100222 / / Medical Research Council / United Kingdom / / Medical Research Council / United Kingdom AG13196 / AG / NIA NIH HHS / United States G8802774 / / Medical Research Council / United Kingdom G0902037 / / Medical Research Council / United Kingdom HHSN268200625226C / / PHS HHS / United States HL36310 / HL / NHLBI NIH HHS / United States HL71862-06 / HL / NHLBI NIH HHS / United States AG032136 / AG / NIA NIH HHS / United States HS06516 / HS / AHRQ HHS / United States N01HC65226-6-0-0 / HC / NHLBI NIH HHS / United States AG034454 / AG / NIA NIH HHS / United States RG/07/008/23674 / / British Heart Foundation / United Kingdom |