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

Fibrinogen is both central to blood coagulation and an acute-phase reactant. We aimed to identify common variants influencing circulation fibrinogen levels.We conducted a genome-wide association analysis on 6 population-based studies, the Rotterdam Study, the Framingham Heart Study, the Cardiovascul...

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Bibliographic Details
Main Authors: Dehghan, A, Yang, Q, Peters, A, Basu, S, Bis, J, Rudnicka, A, Kavousi, M, Chen, M, Baumert, J, Lowe, G, McKnight, B, Tang, W, de Maat, M, Larson, MG, Eyhermendy, S, McArdle, W, Lumley, T, Pankow, J, Hofman, A, Massaro, J, Rivadeneira, F, Kolz, M, Taylor, K, van Duijn, C, Kathiresan, S
Format: Journal article
Language:English
Published: 2009
Description
Summary:Fibrinogen is both central to blood coagulation and an acute-phase reactant. We aimed to identify common variants influencing circulation fibrinogen levels.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)).Our findings highlight biological pathways that may be important in regulation of inflammation underlying cardiovascular disease.