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Gene-centric approach identifies new and known loci for FVIII activity and VWF antigen levels in European Americans and African Americans.
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| Title | Gene-centric approach identifies new and known loci for FVIII activity and VWF antigen levels in European Americans and African Americans. |
| Publication Type | Journal Article |
| Year of Publication | 2015 |
| Authors | Tang, W, Cushman, M, Green, D, Rich, SS, Lange, LA, Yang, Q, Tracy, RP, Tofler, GH, Basu, S, Wilson, JG, Keating, BJ, Weng, L-C, Taylor, HA, Jacobs, DR, Delaney, JA, Palmer, CD, Young, T, Pankow, JS, O'Donnell, CJ, Smith, NL, Reiner, AP, Folsom, AR |
| Journal | Am J Hematol |
| Volume | 90 |
| Issue | 6 |
| Pagination | 534-40 |
| Date Published | 2015 Jun |
| ISSN | 1096-8652 |
| Keywords | Adult, African Americans, Aged, European Continental Ancestry Group, Factor VIII, Female, Genetic Loci, Genome-Wide Association Study, Humans, Male, Methionine Adenosyltransferase, Middle Aged, Polymorphism, Single Nucleotide, Venous Thromboembolism, von Willebrand Factor |
| Abstract | <p>Coagulation factor VIII and von Willebrand factor (VWF) are key proteins in procoagulant activation. Higher FVIII coagulant activity (FVIII :C) and VWF antigen (VWF :Ag) are risk factors for cardiovascular disease and venous thromboembolism. Beyond associations with ABO blood group, genetic determinants of FVIII and VWF are not well understood, especially in non European-American populations. We performed a genetic association study of FVIII :C and VWF:Ag that assessed 50,000 gene-centric single nucleotide polymorphisms (SNPs) in 18,556 European Americans (EAs) and 5,047 African Americans (AAs) from five population-based cohorts. Previously unreported associations for FVIII :C were identified in both AAs and EAs with KNG1 (most significantly associated SNP rs710446, Ile581Thr, Ile581Thr, P = 5.10 × 10(-7) in EAs and P = 3.88 × 10(-3) in AAs) and VWF rs7962217 (Gly2705Arg,P = 6.30 × 10(-9) in EAs and P = 2.98 × 10(-2) in AAs. Significant associations for FVIII :C were also observed with F8/TMLHE region SNP rs12557310 in EAs (P = 8.02 × 10(-10) ), with VWF rs1800380 in AAs (P = 5.62 × 10(-11) ), and with MAT1A rs2236568 in AAs (P51.69 × 10(-6) ). We replicated previously reported associations of FVIII :C and VWF :Ag with the ABO blood group, VWF rs1063856(Thr789Ala), rs216321 (Ala852Gln), and VWF rs2229446 (Arg2185Gln). Findings from this study expand our understanding of genetic influences for FVIII :C and VWF :Ag in both EAs and AAs.</p> |
| DOI | 10.1002/ajh.24005 |
| Alternate Journal | Am. J. Hematol. |
| PubMed ID | 25779970 |
| PubMed Central ID | PMC4747096 |
| Grant List | N01 HC085086 / HC / NHLBI NIH HHS / United States P30 AG024827 / AG / NIA NIH HHS / United States HHSN268201300026C / HL / NHLBI NIH HHS / United States R01 HL075366 / HL / NHLBI NIH HHS / United States R01-HL59367 / HL / NHLBI NIH HHS / United States N01 HC085081 / HC / NHLBI NIH HHS / United States R01 AG015928 / AG / NIA NIH HHS / United States N01 HC095167 / HC / NHLBI NIH HHS / United States N01HC95163 / HL / NHLBI NIH HHS / United States U01 HL080295 / HL / NHLBI NIH HHS / United States N01 HC075150 / HC / NHLBI NIH HHS / United States R01 HL059367 / HL / NHLBI NIH HHS / United States R01 HL095603 / HL / NHLBI NIH HHS / United States N01 HC015103 / HC / NHLBI NIH HHS / United States N01 HC085083 / HC / NHLBI NIH HHS / United States N01HC95169 / HL / NHLBI NIH HHS / United States N01 HC055018 / HC / NHLBI NIH HHS / United States R56 AG020098 / AG / NIA NIH HHS / United States N01 HC025195 / HC / NHLBI NIH HHS / United States N01 HC095161 / HC / NHLBI NIH HHS / United States N01 HC065226 / HC / NHLBI NIH HHS / United States N01 HC085085 / HC / NHLBI NIH HHS / United States N01 HC095164 / HC / NHLBI NIH HHS / United States N01 HC095166 / HC / NHLBI NIH HHS / United States N01HC95164 / HL / NHLBI NIH HHS / United States HHSN268201300025C / HL / NHLBI NIH HHS / United States N01 HC095160 / HC / NHLBI NIH HHS / United States N01HC55222 / HL / NHLBI NIH HHS / United States N01HC95168 / HL / NHLBI NIH HHS / United States R01 DK055017 / DK / NIDDK NIH HHS / United States N01 HC085082 / HC / NHLBI NIH HHS / United States N01 HC055019 / HC / NHLBI NIH HHS / United States N01 HC085080 / HC / NHLBI NIH HHS / United States HHSN268201300027C / HL / NHLBI NIH HHS / United States HHSN268200900041C / HL / NHLBI NIH HHS / United States HHSN268201300028C / HL / NHLBI NIH HHS / United States R01 AG032136 / AG / NIA NIH HHS / United States N01HC95165 / HL / NHLBI NIH HHS / United States N01HC95161 / HL / NHLBI NIH HHS / United States R01 HL080295 / HL / NHLBI NIH HHS / United States R01-HL095603 / HL / NHLBI NIH HHS / United States N01 HC055015 / HC / NHLBI NIH HHS / United States N01 HC055021 / HC / NHLBI NIH HHS / United States N01 HC095165 / HC / NHLBI NIH HHS / United States N01 HC085084 / HC / NHLBI NIH HHS / United States R01 AG020098 / AG / NIA NIH HHS / United States N01HC85082 / HL / NHLBI NIH HHS / United States N01HC95167 / HL / NHLBI NIH HHS / United States N01 HC055020 / HC / NHLBI NIH HHS / United States N01 HC095163 / HC / NHLBI NIH HHS / United States N01 HC085079 / HC / NHLBI NIH HHS / United States N01HC95166 / HL / NHLBI NIH HHS / United States HHSN268201300029C / HL / NHLBI NIH HHS / United States N01 HC095162 / HC / NHLBI NIH HHS / United States R01 AG027058 / AG / NIA NIH HHS / United States N01 HC035129 / HC / NHLBI NIH HHS / United States N01 HC055016 / HC / NHLBI NIH HHS / United States N01 HC095159 / HC / NHLBI NIH HHS / United States |
ePub date:
15/06