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

被引：78

作者：

Dehghan, Abbas ^{[1
,3
]}

Yang, Qiong ^{[2
,3
]}

Peters, Annette ^{[18
]}

Basu, Saonli ^{[6
]}

Bis, Joshua C. ^{[29
]}

Rudnicka, Alicja R. ^{[14
]}

Kavousi, Maryam ^{[1
]}

Chen, Ming-Huei ^{[3
,4
,5
]}

Baumert, Jens ^{[18
]}

Lowe, Gordon D. O. ^{[16
]}

McKnight, Barbara ^{[26
]}

Tang, Weihong ^{[10
]}

de Maat, Moniek ^{[7
]}

Larson, Martin G. ^{[2
,9
]}

Eyhermendy, Susana ^{[24
]}

McArdle, Wendy L. ^{[15
]}

Lumley, Thomas ^{[26
]}

Pankow, James S. ^{[10
]}

Hofman, Albert ^{[1
]}

Massaro, Joseph M. ^{[2
,9
]}

Rivadeneira, Fernando ^{[8
]}

Kolz, Melanie ^{[18
]}

Taylor, Kent D. ^{[30
]}

van Duijn, Cornelia M. ^{[1
]}

Kathiresan, Sekar ^{[2
,20
,21
]}

Illig, Thomas ^{[18
]}

Aulchenko, Yurii S. ^{[1
]}

Volcik, Kelly A. ^{[11
,12
]}

Johnson, Andrew D. ^{[2
,31
]}

Uitterlinden, Andre G. ^{[8
]}

Tofler, Geoffrey H. ^{[22
]}

Gieger, Christian ^{[18
]}

Psaty, Bruce M. ^{[27
,28
,29
]}

Couper, David J. ^{[13
]}

Boerwinkle, Eric ^{[11
,12
]}

Koenig, Wolfgang ^{[23
]}

O'Donnell, Christopher J. ^{[2
,19
,31
]}

Witteman, Jacqueline C. ^{[1
]}

Strachan, David P. ^{[14
]}

Smith, Nicholas L. ^{[25
,27
]}

Folsom, Aaron R. ^{[10
]}

机构：

[1] Erasmus MC, Dept Epidemiol, NL-3000 CA Rotterdam, Netherlands

[2] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA

[3] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA

[4] Boston Univ, Dept Neurol, Boston, MA 02215 USA

[5] Boston Univ, Framingham Heart Study, Boston, MA 02215 USA

[6] Univ Minnesota, Div Biostat, Minneapolis, MN USA

[7] Erasmus MC, Dept Hematol, NL-3000 CA Rotterdam, Netherlands

[8] Erasmus MC, Dept Internal Med, NL-3000 CA Rotterdam, Netherlands

[9] Boston Univ, Dept Math, Boston, MA 02215 USA

[10] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA

[11] Univ Texas Hlth Sci Ctr, Ctr Human Genet, Houston, TX USA

[12] Univ Texas Hlth Sci Ctr, Inst Mol Med, Houston, TX USA

[13] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA

[14] Univ London, Div Community Hlth Sci, London, England

[15] Univ Bristol, ALSPAC Lab, Bristol, Avon, England

[16] Univ Glasgow, Royal Infirm, Div Cardiovasc & Med Sci, Glasgow, Lanark, Scotland

[17] Wellcome Trust Res Labs, Cambridge, England

[18] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol, Neuherberg, Germany

[19] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA

[20] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA USA

[21] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA USA

[22] Royal N Shore Hosp, Sydney, NSW, Australia

[23] Univ Ulm, Dept Internal Med Cardiol 2, Ulm, Germany

[24] Pontificia Univ Catolica Chile, Dept Stat, Santiago, Chile

[25] Vet Affairs Off Res & Dev, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA

[26] Univ Washington, Dept Biostat, Seattle, WA 98195 USA

[27] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA

[28] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA

[29] Univ Washington, Dept Med, Seattle, WA USA

[30] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA

[31] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA

来源：

CIRCULATION-CARDIOVASCULAR GENETICS | 2009年 / 2卷 / 02期

基金：

美国国家卫生研究院;

关键词：

genome-wide association study; fibrinogen; genes; meta-analysis; INFLAMMATORY-BOWEL-DISEASE; CARDIOVASCULAR-DISEASE; VENOUS THROMBOSIS; PLASMA-FIBRINOGEN; FRAMINGHAM; DESIGN; RISK; EXPRESSION; HEART; OBJECTIVES;

D O I：

10.1161/CIRCGENETICS.108.825224

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：125 / U91

页数：17

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