Browsing by Author "Rudnicka, Alicja R."

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    Association of Novel Genetic Loci With Circulating Fibrinogen Levels A Genome-Wide Association Study in 6 Population-Based Cohorts
    (LIPPINCOTT WILLIAMS & WILKINS, 2009) Dehghan, Abbas; Yang, Qiong; Peters, Annette; Basu, Saonli; Bis, Joshua C.; Rudnicka, Alicja R.; Kavousi, Maryam; Chen, Ming Huei; Baumert, Jens; Lowe, Gordon D. O.; McKnight, Barbara; Tang, Weihong; de Maat, Moniek; Larson, Martin G.; Eyhermendy, Susana; McArdle, Wendy L.; Lumley, Thomas; Pankow, James S.; Hofman, Albert; Massaro, Joseph M.; Rivadeneira, Fernando; Kolz, Melanie; Taylor, Kent D.; van Duijn, Cornelia M.; Kathiresan, Sekar; Illig, Thomas; Aulchenko, Yurii S.; Volcik, Kelly A.; Johnson, Andrew D.; Uitterlinden, Andre G.; Tofler, Geoffrey H.; Gieger, Christian; Psaty, Bruce M.; Couper, David J.; Boerwinkle, Eric; Koenig, Wolfgang; O'Donnell, Christopher J.; Witteman, Jacqueline C.; Strachan, David P.; Smith, Nicholas L.; Folsom, Aaron R.; Wellcome Trust Case Control Consor
    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.