Assessment of Genetic Determinants of the Association of γ′ Fibrinogen in Relation to Cardiovascular Disease

Abstract

γ′ fibrinogen is a newly emerging biomarker that is associated with cardiovascular disease (CVD). However, the genetic determinants of γ′ fibrinogen levels are unknown. We therefore conducted a genome-wide association study on 3042 participants from the Framingham Heart Study Offspring Cohort. A genome-wide association study with 2.5 million single-nucleotide polymorphisms (SNPs) was carried out for γ′ fibrinogen levels from the cycle 7 examination. Fifty-four SNPs in or near the fibrinogen gene locus demonstrated genome-wide significance ( P −8 ) for association with γ′ fibrinogen levels. The top-signal SNP was rs7681423 ( P =9.97×10 ⁻¹¹⁰ ) in the fibrinogen gene locus near FGG , which encodes the γ chain. Conditional on the top SNP, the only other SNP that remained genome-wide significant was rs1049636. Associations between SNPs, γ′ fibrinogen levels, and prevalent CVD events were examined using multiple logistic regression. γ′ fibrinogen levels were associated with prevalent CVD ( P =0.02), although the top 2 SNPs associated with γ′ fibrinogen levels were not associated with CVD. These findings contrast those for total fibrinogen levels, which are associated with different genetic loci, particularly FGB , which encodes the Bβ chain. γ′ fibrinogen is associated with prevalent CVD and with SNPs exclusively in and near the fibrinogen gene locus.