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

Abbas Dehghan; 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; 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; Wellcome Trust Case Control Consortium

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
, 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, 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, Wellcome Trust Case Control Consortium

Bristol Medical School (PHS)

Research output: Contribution to journal › Article (Academic Journal) › peer-review

88 Citations (Scopus)

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<5.0×10⁻⁸). 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.

Original language	English
Pages (from-to)	125-133
Number of pages	9
Journal	Circulation: Cardiovascular Genetics
Volume	2
Issue number	2
Early online date	14 Apr 2009
DOIs	https://doi.org/10.1161/CIRCGENETICS.108.825224
Publication status	Published - Apr 2009

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

genome-wide association study
fibrinogen
genes
meta-analysis

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10.1161/CIRCGENETICS.108.825224

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Dehghan, A., Yang, Q., Peters, A., Basu, S., Bis, J. C., Rudnicka, A. R., Kavousi, M., Chen, M.-H., Baumert, J., Lowe, G. D. O., McKnight, B., Tang, W., de Maat, M., Larson, M. G., Eyhermendy, S., McArdle, W. L., Lumley, T., Pankow, J. S., Hofman, A., ... Wellcome Trust Case Control Consortium (2009). Association of Novel Genetic Loci With Circulating Fibrinogen Levels: A Genome-Wide Association Study in 6 Population-Based Cohorts. Circulation: Cardiovascular Genetics, 2(2), 125-133. https://doi.org/10.1161/CIRCGENETICS.108.825224

@article{79bd7f19aa434510bd5e60a5b09276fa,

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

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<5.0×10−8). 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.",

keywords = "genome-wide association study, fibrinogen, genes, meta-analysis",

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

year = "2009",

month = apr,

doi = "10.1161/CIRCGENETICS.108.825224",

language = "English",

volume = "2",

pages = "125--133",

journal = "Circulation: Cardiovascular Genetics",

issn = "1942-325X",

publisher = "Lippincott Williams and Wilkins",

number = "2",

}

Dehghan, 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 & Wellcome Trust Case Control Consortium 2009, 'Association of Novel Genetic Loci With Circulating Fibrinogen Levels: A Genome-Wide Association Study in 6 Population-Based Cohorts', Circulation: Cardiovascular Genetics, vol. 2, no. 2, pp. 125-133. https://doi.org/10.1161/CIRCGENETICS.108.825224

TY - JOUR

T1 - Association of Novel Genetic Loci With Circulating Fibrinogen Levels

T2 - A Genome-Wide Association Study in 6 Population-Based Cohorts

AU - Dehghan, Abbas

AU - Yang, Qiong

AU - Peters, Annette

AU - Basu, Saonli

AU - Bis, Joshua C

AU - Rudnicka, Alicja R

AU - Kavousi, Maryam

AU - Chen, Ming-Huei

AU - Baumert, Jens

AU - Lowe, Gordon D O

AU - McKnight, Barbara

AU - Tang, Weihong

AU - de Maat, Moniek

AU - Larson, Martin G

AU - Eyhermendy, Susana

AU - McArdle, Wendy L

AU - Lumley, Thomas

AU - Pankow, James S

AU - Hofman, Albert

AU - Massaro, Joseph M

AU - Rivadeneira, Fernando

AU - Kolz, Melanie

AU - Taylor, Kent D

AU - van Duijn, Cornelia M

AU - Kathiresan, Sekar

AU - Illig, Thomas

AU - Aulchenko, Yurii S

AU - Volcik, Kelly A

AU - Johnson, Andrew D

AU - Uitterlinden, Andre G

AU - Tofler, Geoffrey H

AU - Gieger, Christian

AU - Psaty, Bruce M

AU - Couper, David J

AU - Boerwinkle, Eric

AU - Koenig, Wolfgang

AU - O'Donnell, Christopher J

AU - Witteman, Jacqueline C

AU - Strachan, David P

AU - Smith, Nicholas L

AU - Folsom, Aaron R

AU - Wellcome Trust Case Control Consortium

PY - 2009/4

Y1 - 2009/4

N2 - 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.

AB - 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.

KW - genome-wide association study

KW - fibrinogen

KW - genes

KW - meta-analysis

U2 - 10.1161/CIRCGENETICS.108.825224

DO - 10.1161/CIRCGENETICS.108.825224

M3 - Article (Academic Journal)

C2 - 20031576

SN - 1942-325X

VL - 2

SP - 125

EP - 133

JO - Circulation: Cardiovascular Genetics

JF - Circulation: Cardiovascular Genetics

IS - 2

ER -

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

Abstract

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