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

Circ Cardiovasc Genet. 2009 Apr;2(2):125-33. doi: 10.1161/CIRCGENETICS.108.825224.

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 x 10(-8)). These included a single-nucleotide polymorphism located in the fibrinogen beta 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 x 10(-30)), rs2522056 downstream from the interferon regulatory factor 1 (IRF1) gene (P=1.3 x 10(-15)), rs511154 within intron 1 of the propionyl coenzyme A carboxylase (PCCB) gene (P=5.9 x 10(-10)), and rs1539019 on the NLR family pyrin domain containing 3 isoforms (NLRP3) gene (P=1.04 x 10(-8)).

Conclusions: Our findings highlight biological pathways that may be important in regulation of inflammation underlying cardiovascular disease.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / genetics*
  • Cohort Studies
  • European Continental Ancestry Group / genetics
  • Female
  • Fibrinogen / genetics*
  • Fibrinogen / metabolism*
  • Genetic Loci*
  • Genome-Wide Association Study*
  • Humans
  • Male
  • Middle Aged
  • Pedigree
  • Polymorphism, Single Nucleotide
  • Young Adult

Substances

  • Fibrinogen