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

Objective-gamma ' fibrinogen is a newly emerging biomarker that is associated with cardiovascular disease (CVD). However, the genetic determinants of gamma ' fibrinogen levels are unknown. We therefore conducted a genome-wide association study on 3042 participants from the Framingham Heart Study Offspring Cohort. Methods and Results-A genome-wide association study with 2.5 million single-nucleotide polymorphisms (SNPs) was carried out for gamma ' fibrinogen levels from the cycle 7 examination. Fifty-four SNPs in or near the fibrinogen gene locus demonstrated genome-wide significance (P<5.0x10(-8)) for association with gamma ' fibrinogen levels. The top-signal SNP was rs7681423 (P=9.97x10(-110)) in the fibrinogen gene locus near FGG, which encodes the gamma chain. Conditional on the top SNP, the only other SNP that remained genome-wide significant was rs1049636. Associations between SNPs, gamma ' fibrinogen levels, and prevalent CVD events were examined using multiple logistic regression. gamma ' fibrinogen levels were associated with prevalent CVD (P=0.02), although the top 2 SNPs associated with gamma ' 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 B beta chain. Conclusion-gamma ' fibrinogen is associated with prevalent CVD and with SNPs exclusively in and near the fibrinogen gene locus. (Arterioscler Thromb Vasc Biol. 2011;31:2345-2352.)