Association of novel genetic Loci with circulating fibrinogen levels: a genome-wide association study in 6 population-based cohorts.
BACKGROUND
Fibrinogen is both central to blood coagulation and an acute-phase reactant. We aimed to identify common variants influencing circulation fibrinogen levels.


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.
Dehghan
Abbas
A
Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
Yang
Qiong
Q
Peters
Annette
A
Basu
Saonli
S
Bis
Joshua C
JC
Rudnicka
Alicja R
AR
Kavousi
Maryam
M
Chen
Ming-Huei
MH
Baumert
Jens
J
Lowe
Gordon D O
GD
McKnight
Barbara
B
Tang
Weihong
W
de Maat
Moniek
M
Larson
Martin G
MG
Eyhermendy
Susana
S
McArdle
Wendy L
WL
Lumley
Thomas
T
Pankow
James S
JS
Hofman
Albert
A
Massaro
Joseph M
JM
Rivadeneira
Fernando
F
Kolz
Melanie
M
Taylor
Kent D
KD
van Duijn
Cornelia M
CM
Kathiresan
Sekar
S
Illig
Thomas
T
Aulchenko
Yurii S
YS
Volcik
Kelly A
KA
Johnson
Andrew D
AD
Uitterlinden
Andre G
AG
Tofler
Geoffrey H
GH
Gieger
Christian
C
Psaty
Bruce M
BM
Couper
David J
DJ
Boerwinkle
Eric
E
Koenig
Wolfgang
W
O'Donnell
Christopher J
CJ
Witteman
Jacqueline C
JC
Strachan
David P
DP
Smith
Nicholas L
NL
Folsom
Aaron R
AR
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002318:Cardiovascular Diseases / Q000097:blood / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D005340:Fibrinogen / Q000235:genetics* / Q000378:metabolism*; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics; D055815:Young Adult
D005340:Fibrinogen