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Circulation: Cardiovascular Genetics

Year: 2009  |  Volume: 2  |  Issue: 2  |  Page No.: 125 - 133

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

A Dehghan, Q Yang, A Peters, S Basu, J. C Bis, A. R Rudnicka, M Kavousi, M. H Chen, J Baumert, G. D.O Lowe, B McKnight, W Tang, M de Maat, M. G Larson, S Eyhermendy, W. L McArdle, T Lumley, J. S Pankow, A Hofman, J. M Massaro, F Rivadeneira, M Kolz, K. D Taylor, C. M van Duijn, S Kathiresan, T Illig, Y. S Aulchenko, K. A Volcik, A. D Johnson, A. G Uitterlinden, G. H Tofler, C Gieger, Psaty Wellcome Trust Case Control Consortium, D. J Couper, E Boerwinkle, W Koenig, C. J O`Donnell, J. C Witteman, D. P Strachan, N. L Smith and A. R. Folsom

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<5.0x10–8). 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=1.8x10–30), rs2522056 downstream from the interferon regulatory factor 1 (IRF1) gene (P=1.3x10–15), rs511154 within intron 1 of the propionyl coenzyme A carboxylase (PCCB) gene (P=5.9x10–10), and rs1539019 on the NLR family pyrin domain containing 3 isoforms (NLRP3) gene (P=1.04x10–8).

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

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