Association of novel genetic loci with circulating fibrinogen levels a genome-wide association study in 6 population-based cohorts

Abbas Dehghan, Qiong Yang, Annette Peters, Saonli Basu, Joshua C. Bis, Alicja R. Rudnicka, Maryam Kavousi, Ming Huei Chen, Jens Baumert, Gordon D O Lowe, Barbara McKnight, Weihong Tang, Moniek De Maat, Martin G. Larson, Susana Eyhermendy, Wendy L. McArdle, Thomas Lumley, James S. Pankow, Albert Hofman, Joseph M. MassaroFernando Rivadeneira, Melanie Kolz, Kent D. Taylor, Cornelia M. Van Duijn, Sekar Kathiresan, Thomas Illig, Yurii S. Aulchenko, Kelly A. Volcik, Andrew D. Johnson, Andre G. Uitterlinden, Geoffrey H. Tofler, Christian Gieger, Bruce M. Psaty, David J. Couper, Eric Boerwinkle, Wolfgang Koenig, Christopher J. O'Donnell, Jacqueline C. Witteman, David P. Strachan, Nicholas L. Smith, Aaron R. Folsom

Research output: Contribution to journalArticlepeer-review

77 Scopus citations

Abstract

Background: Fibrinogen is both central to blood coagulation and an acute-phase reactant. We aimed to identify common variants influencing circulation fibrinogen levels. Methods and Results: We conducted a genome-wide association analysis on 6 population-based studies, the Rotterdam Study, the Framingham Heart Study, the Cardiovascular Health Study, the Atherosclerosis Risk in Communities Study, the Monitoring of Trends and Determinants in Cardiovascular Disease/KORA Augsburg Study, and the British 1958 Birth Cohort Study, including 22 096 participants of European ancestry. Four loci were marked by 1 or more single-nucleotide polymorphisms that demonstrated genome-wide significance (P<5.0×10-8). These included a single-nucleotide polymorphism located in the fibrinogen β chain (FGB) gene and 3 single-nucleotide polymorphisms representing newly identified loci. The high-signal single-nucleotide polymorphisms were rs1800789 in exon 7 of FGB (P=1.8×10-30), rs2522056 downstream from the interferon regulatory factor 1 (IRF1) gene (P=1.3×10-15), rs511154 within intron 1 of the propionyl coenzyme A carboxylase (PCCB) gene (P=5.9×10-10), and rs1539019 on the NLR family pyrin domain containing 3 isoforms (NLRP3) gene (P=1.04×10-8). Conclusions: Our findings highlight biological pathways that may be important in regulation of inflammation underlying cardiovascular disease.

Original languageEnglish (US)
Pages (from-to)125-133
Number of pages9
JournalCirculation: Cardiovascular Genetics
Volume2
Issue number2
DOIs
StatePublished - Apr 2009

Keywords

  • Fibrinogen
  • Genes
  • Genome-wide association study
  • Meta-analysis

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