Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2009 Apr;2(2):125-33.
doi: 10.1161/CIRCGENETICS.108.825224.

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

Abbas Dehghan  1 , Qiong Yang, Annette Peters, Saonli Basu, Joshua C Bis, Alicja R Rudnicka, Maryam Kavousi, Ming-Huei Chen, Jens Baumert, Gordon D O Lowe, Barbara McKnight, Weihong Tang, Moniek de Maat, Martin G Larson, Susana Eyhermendy, Wendy L McArdle, Thomas Lumley, James S Pankow, Albert Hofman, Joseph M Massaro, Fernando Rivadeneira, Melanie Kolz, Kent D Taylor, Cornelia M van Duijn, Sekar Kathiresan, Thomas Illig, Yurii S Aulchenko, Kelly A Volcik, Andrew D Johnson, Andre G Uitterlinden, Geoffrey H Tofler, Christian Gieger; Wellcome Trust Case Control Consortium; Bruce M Psaty, David J Couper, Eric Boerwinkle, Wolfgang Koenig, Christopher J O'Donnell, Jacqueline C Witteman, David P Strachan, Nicholas L Smith, Aaron R Folsom
Collaborators, Affiliations
Meta-Analysis

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

Abbas Dehghan et al. Circ Cardiovasc Genet. 2009 Apr.

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.

PubMed Disclaimer

Figures

Figure 1
Figure 1
QQ-plot for the meta-analysis results. Quantile-quantile plot of the observed and the expected distribution of p-values for all 2,661,766 SNPs and their association with fibrinogen levels based on meta-analyzed data.
Figure 2
Figure 2
−Log plot for the meta-analysis. −Log p-values for each of the 2,661,766 tests performed as part of the genome-wide association analysis of fibrinogen levels. The grey dashed horizontal lines correspond to the p-value threshold of 5×10−8 and the grey solid line corresponds to 5×10−6.
Figure 3
Figure 3
Regional plots of loci associated with fibrinogen. (a-d). The association p-values (−log10 transformed, indicated by the left y-axis) for SNPs in a 60kb region of each of the four loci (FGB, IRF1, PCCB, NLRP3) are plotted against their chromosome positions (NCBI build 36) on x-axis. Each diamond represents a SNP with the color indicating the linkage disequilibrium (estimated using HapMap CEU sample) between the SNP and the top associated SNP that is plotted by a red diamond with size larger than all other diamonds, and with the SNP name displayed on the top, and p-value on the right. Shown in light blue are the estimated recombination rates in HapMap with values indicated by the right y-axis. The bottom panel displays the genes in the region based on the UCSC Genome Browser March 2006 assembly, with the arrow to right (left) indicate indicating +(−) strand. The grey horizontal line corresponds to the p-value threshold of genome-wide significance, 5×10−8.
See this image and copyright information in PMC

References

Web Resources

    1. MACH http://www.sph.umich.edu/csg/abecasis/MACH/index.html
    1. SHARE http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs0...
    1. SNPTEST http://www.stats.ox.ac.uk/marchini/software/gwas/snptest.html
    1. R-project http://www.r-project.org
    1. MetABEL http://mga.bionet.nsc.ru/~yurii/ABEL

References

    1. Danesh J, Lewington S, Thompson SG, Lowe GD, Collins R, Kostis JB, Wilson AC, Folsom AR, Wu K, Benderly M, Goldbourt U, Willeit J, Kiechl S, Yarnell JW, Sweetnam PM, Elwood PC, Cushman M, Psaty BM, Tracy RP, Tybjaerg-Hansen A, Haverkate F, de Maat MP, Fowkes FG, Lee AJ, Smith FB, Salomaa V, Harald K, Rasi R, Vahtera E, Jousilahti P, Pekkanen J, D'Agostino R, Kannel WB, Wilson PW, Tofler G, Arocha-Pinango CL, Rodriguez-Larralde A, Nagy E, Mijares M, Espinosa R, Rodriquez-Roa E, Ryder E, Diez-Ewald MP, Campos G, Fernandez V, Torres E, Marchioli R, Valagussa F, Rosengren A, Wilhelmsen L, Lappas G, Eriksson H, Cremer P, Nagel D, Curb JD, Rodriguez B, Yano K, Salonen JT, Nyyssonen K, Tuomainen TP, Hedblad B, Lind P, Loewel H, Koenig W, Meade TW, Cooper JA, De Stavola B, Knottenbelt C, Miller GJ, Bauer KA, Rosenberg RD, Sato S, Kitamura A, Naito Y, Palosuo T, Ducimetiere P, Amouyel P, Arveiler D, Evans AE, Ferrieres J, Juhan-Vague I, Bingham A, Schulte H, Assmann G, Cantin B, Lamarche B, Despres JP, Dagenais GR, Tunstall-Pedoe H, Woodward M, Ben-Shlomo Y, Davey Smith G, Palmieri V, Yeh JL, Rudnicka A, Ridker P, Rodeghiero F, Tosetto A, Shepherd J, Ford I, Robertson M, Brunner E, Shipley M, Feskens EJ, Kromhout D, Dickinson A, Ireland B, Juzwishin K, Kaptoge S, Memon A, Sarwar N, Walker M, Wheeler J, White I, Wood A. Plasma fibrinogen level and the risk of major cardiovascular diseases and nonvascular mortality: an individual participant meta-analysis. Jama. 2005;294:1799–809. - PubMed
    1. Yang Q, Tofler GH, Cupples LA, Larson MG, Feng D, Lindpaintner K, Levy D, D'Agostino RB, O'Donnell CJ. A genome-wide search for genes affecting circulating fibrinogen levels in the Framingham Heart Study. Thromb Res. 2003;110:57–64. - PubMed
    1. de Lange M, Snieder H, Ariens RA, Spector TD, Grant PJ. The genetics of haemostasis: a twin study. Lancet. 2001;357:101–5. - PubMed
    1. Kathiresan S, Yang Q, Larson MG, Camargo AL, Tofler GH, Hirschhorn JN, Gabriel SB, O'Donnell CJ. Common genetic variation in five thrombosis genes and relations to plasma hemostatic protein level and cardiovascular disease risk. Arterioscler Thromb Vasc Biol. 2006;26:1405–12. - PubMed
    1. Psaty BM, OD C, Gudnason V, Lunetta KL, Folsom AR, Rotter JI, Uitterlinden AG, Harris TB, Witteman JCM, Boerwinkle E, on behalf of the CHARGE Consortium Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium: Design of prospective meta-analyses of genome-wide association studies from five cohorts. Circ Cardiovasc Genet. In Press. - PMC - PubMed

Publication types

Grants and funding