Association of Novel Genetic Loci With Circulating Fibrinogen Levels A Genome-Wide Association Study in 6 Population-Based Cohorts

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. © 2009 American Heart Association, Inc.