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, Wellcome Trust Case Control Consortium

Research output: Contribution to journalArticle (Academic Journal)peer-review

77 Citations (Scopus)

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
Pages (from-to)125-133
Number of pages9
JournalCirculation: Cardiovascular Genetics
Volume2
Issue number2
Early online date14 Apr 2009
DOIs
Publication statusPublished - Apr 2009

Keywords

  • genome-wide association study
  • fibrinogen
  • genes
  • meta-analysis

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