Association of genomic loci from a cardiovascular gene SNP array with fibrinogen levels in European Americans and African-Americans from six cohort studies: the Candidate Gene Association Resource (CARe).
Several common genomic loci, involving various immunity- and metabolism-related genes, have been associated with plasma fibrinogen in European Americans (EAs). The genetic determinants of fibrinogen in African Americans (AAs) are poorly characterized. Using a vascular gene-centric array in 23,634 EA and 6657 AA participants from 6 studies comprising the Candidate Gene Association Resource project, we examined the association of 47,539 common and lower frequency variants with fibrinogen concentration. We identified a rare Pro265Leu variant in FGB (rs6054) associated with lower fibrinogen. Common fibrinogen gene single nucleotide polymorphisms (FGB rs1800787 and FGG rs2066861) significantly associated with fibrinogen in EAs were prevalent in AAs and showed consistent associations. Several fibrinogen locus single nucleotide polymorphism associated with lower fibrinogen were exclusive to AAs; these include a newly reported association with FGA rs10050257. For IL6R, IL1RN, and NLRP3 inflammatory gene loci, associations with fibrinogen were concordant between EAs and AAs, but not at other loci (CPS1, PCCB, and SCL22A5-IRF1). The association of FGG rs2066861 with fibrinogen differed according to assay type used to measure fibrinogen. Further characterization of common and lower-frequency genetic variants that contribute to interpopulation differences in fibrinogen phenotype may help refine our understanding of the contribution of hemostasis and inflammation to atherothrombotic risk.
University of California, San Diego, CA, USA.
Christina L
CL
Wassel
Leslie A
LA
Lange
Brendan J
BJ
Keating
Kira C
KC
Taylor
Andrew D
AD
Johnson
Cameron
C
Palmer
Lindsey A
LA
Ho
Nicholas L
NL
Smith
Ethan M
EM
Lange
Yun
Y
Li
Qiong
Q
Yang
Joseph A
JA
Delaney
Weihong
W
Tang
Geoffrey
G
Tofler
Susan
S
Redline
Herman A
HA
Taylor
James G
JG
Wilson
Russell P
RP
Tracy
David R
DR
Jacobs
Aaron R
AR
Folsom
David
D
Green
Christopher J
CJ
O'Donnell
Alexander P
AP
Reiner
D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000368:Aged; D002318:Cardiovascular Diseases / Q000097:blood / Q000208:ethnology* / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D005340:Fibrinogen / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D044465:White People / Q000235:genetics*
D005340:Fibrinogen