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

Tuesday,2012-11-06 12:19 America/Los_Angeles — eenright
TitleAssociation of novel genetic Loci with circulating fibrinogen levels: a genome-wide association study in 6 population-based cohorts.
Publication TypeJournal Article
Year of Publication2009
AuthorsDehghan, A, Yang, Q, Peters, A, Basu, S, Bis, JC, Rudnicka, AR, Kavousi, M, Chen, M-H, Baumert, J, Lowe, GDO, McKnight, B, Tang, W, de Maat, M, Larson, MG, Eyhermendy, S, McArdle, WL, Lumley, T, Pankow, JS, Hofman, A, Massaro, JM, Rivadeneira, F, Kolz, M, Taylor, KD, van Duijn, CM, Kathiresan, S, Illig, T, Aulchenko, YS, Volcik, KA, Johnson, AD, Uitterlinden, AG, Tofler, GH, Gieger, C, Psaty, BM, Couper, DJ, Boerwinkle, E, Koenig, W, O'Donnell, CJ, Witteman, JC, Strachan, DP, Smith, NL, Folsom, AR
Corporate/Institutional AuthorsWellcome Trust Case Control Consortium,
JournalCirc Cardiovasc Genet
Volume2
Issue2
Pagination125-33
Date Published2009 Apr
ISSN1942-3268
KeywordsAdult, Aged, Aged, 80 and over, Cardiovascular Diseases, Cohort Studies, European Continental Ancestry Group, Female, Fibrinogen, Genetic Loci, Genome-Wide Association Study, Humans, Male, Middle Aged, Pedigree, Polymorphism, Single Nucleotide, Young Adult
Abstract<p><b>BACKGROUND: </b>Fibrinogen is both central to blood coagulation and an acute-phase reactant. We aimed to identify common variants influencing circulation fibrinogen levels.</p><p><b>METHODS AND RESULTS: </b>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)).</p><p><b>CONCLUSIONS: </b>Our findings highlight biological pathways that may be important in regulation of inflammation underlying cardiovascular disease.</p>
DOI10.1161/CIRCGENETICS.108.825224
Alternate JournalCirc Cardiovasc Genet
PubMed ID20031576
PubMed Central IDPMC2764985
Grant ListN01HC55020 / HL / NHLBI NIH HHS / United States
N01-HC-25195 / HC / NHLBI NIH HHS / United States
N01 HC055022 / HC / NHLBI NIH HHS / United States
HL073410 / HL / NHLBI NIH HHS / United States
N01 HC085086 / HC / NHLBI NIH HHS / United States
P30 DK063491-05 / DK / NIDDK NIH HHS / United States
R01-HL-086694 / HL / NHLBI NIH HHS / United States
G0701003 / / Medical Research Council / United Kingdom
N01HC55018 / HL / NHLBI NIH HHS / United States
N01-HC-85085 / HC / NHLBI NIH HHS / United States
R01 HL087652-03 / HL / NHLBI NIH HHS / United States
UL1 RR025005 / RR / NCRR NIH HHS / United States
UL1-RR-025005 / RR / NCRR NIH HHS / United States
HHS N268200625226C / / PHS HHS / United States
U01 HL080295 / HL / NHLBI NIH HHS / United States
N01 HC075150 / HC / NHLBI NIH HHS / United States
N01-HC-55022 / HC / NHLBI NIH HHS / United States
N01-HC-85081 / HC / NHLBI NIH HHS / United States
R01 HL059367 / HL / NHLBI NIH HHS / United States
R01-HL-087641 / HL / NHLBI NIH HHS / United States
U01 HL080295-05 / HL / NHLBI NIH HHS / United States
N01 HC015103 / HC / NHLBI NIH HHS / United States
N01-HC-55016 / HC / NHLBI NIH HHS / United States
N01 HC055018 / HC / NHLBI NIH HHS / United States
R01 HL073410-04 / HL / NHLBI NIH HHS / United States
N01 HC025195 / HC / NHLBI NIH HHS / United States
R01 HL086694 / HL / NHLBI NIH HHS / United States
N02 HL64278 / HL / NHLBI NIH HHS / United States
R01 HL087652 / HL / NHLBI NIH HHS / United States
U01 HG004402 / HG / NHGRI NIH HHS / United States
N01HC55022 / HL / NHLBI NIH HHS / United States
N01HC55222 / HL / NHLBI NIH HHS / United States
N01-HC-55021 / HC / NHLBI NIH HHS / United States
N01-HC-85086 / HC / NHLBI NIH HHS / United States
R01 HL087652-02 / HL / NHLBI NIH HHS / United States
N01HC55015 / HL / NHLBI NIH HHS / United States
N01HC85086 / HL / NHLBI NIH HHS / United States
P30 DK063491-039004 / DK / NIDDK NIH HHS / United States
N01-HC-85082 / HC / NHLBI NIH HHS / United States
R01-HL-59367 / HL / NHLBI NIH HHS / United States
N01 HC055019 / HC / NHLBI NIH HHS / United States
R01 HL087641-03 / HL / NHLBI NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
R01 HL086694-02 / HL / NHLBI NIH HHS / United States
N01 HC-55222 / HC / NHLBI NIH HHS / United States
N01-HC-55019 / HC / NHLBI NIH HHS / United States
N01-HC-55015 / HC / NHLBI NIH HHS / United States
N01 HC055222 / HC / NHLBI NIH HHS / United States
R01 HL 087652 / HL / NHLBI NIH HHS / United States
G0800759 / / Medical Research Council / United Kingdom
M01RR00069 / RR / NCRR NIH HHS / United States
N01-HC-85083 / HC / NHLBI NIH HHS / United States
090532 / / Wellcome Trust / United Kingdom
N01-HC-75150 / HC / NHLBI NIH HHS / United States
N01-HC-55020 / HC / NHLBI NIH HHS / United States
N01-HC-85080 / HC / NHLBI NIH HHS / United States
N01HC55016 / HL / NHLBI NIH HHS / United States
P30 DK063491-029004 / DK / NIDDK NIH HHS / United States
CZB/4/540 / / Chief Scientist Office / United Kingdom
N01 HC055015 / HC / NHLBI NIH HHS / United States
N01 HC055021 / HC / NHLBI NIH HHS / United States
N01HC55019 / HL / NHLBI NIH HHS / United States
N01HC75150 / HL / NHLBI NIH HHS / United States
P30 DK063491-019004 / DK / NIDDK NIH HHS / United States
N01HC25195 / HL / NHLBI NIH HHS / United States
DK063491 / DK / NIDDK NIH HHS / United States
N01-HC-85079 / HC / NHLBI NIH HHS / United States
R01 HL059367-09 / HL / NHLBI NIH HHS / United States
N01 HC055020 / HC / NHLBI NIH HHS / United States
068545/Z/02 / / Wellcome Trust / United Kingdom
P30 DK063491-049004 / DK / NIDDK NIH HHS / United States
MC_QA137934 / / Medical Research Council / United Kingdom
N01HC85079 / HL / NHLBI NIH HHS / United States
N01 HC085079 / HC / NHLBI NIH HHS / United States
N02-HL-64278 / HL / NHLBI NIH HHS / United States
N01-HC-55018 / HC / NHLBI NIH HHS / United States
N01HC55021 / HL / NHLBI NIH HHS / United States
R01 HL087641 / HL / NHLBI NIH HHS / United States
U01-HG-004402 / HG / NHGRI NIH HHS / United States
R01 HL073410 / HL / NHLBI NIH HHS / United States
061858 / / Wellcome Trust / United Kingdom
N01 HC045133 / HC / NHLBI NIH HHS / United States
G0000934 / / Medical Research Council / United Kingdom
G0800675 / / Medical Research Council / United Kingdom
N01 HC035129 / HC / NHLBI NIH HHS / United States
N01 HC055016 / HC / NHLBI NIH HHS / United States
N01-HC-85084 / HC / NHLBI NIH HHS / United States
G0600329 / / Medical Research Council / United Kingdom
U01 HG004402-02 / HG / NHGRI NIH HHS / United States

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