"The proposed project aims at the identification and characterization of novel genes, genetic variants and pathways implicated in the regulation of plasma fibrinogen concentration, which is an independent risk factor for cardiovascular disease (CVD). Several genome-wide linkage and association studies have identified some interesting regions which may contain candidate genes that are not yet identified. Despite this exciting progress in narrowing down genomic regions that may be linked to plasma fibrinogen concentration, very few of these signals have actually been dissected to the final causative gene that is responsible for disease susceptibility, and in most instances, the allelic variants and the biological mechanisms underlying these signals remain unknown. Thus, our first and main objective is to dissect already defined candidate regions to identify attractive novel candidate genes and variants that explain variation in plasma fibrinogen concentration. Specifically, we will exploit the novel “expression QTL” methodology as our main tool to prioritize candidate genes in previously described chromosomal regions associated with plasma fibrinogen concentration. This new strategy allows the identification of transcriptional regulatory loci without any prior knowledge of the regulatory mechanism and is now gaining increasing attention as a powerful tool to understand the molecular networks in which candidate genes operate and how changes in these networks lead to changes in disease traits. Accordingly, we expect that it may reveal important novel information about the mechanisms and biological pathways by which some genetic variants may affect plasma fibrinogen regulation. The identification of genes, genetic variants and pathways that influence plasma fibrinogen concentration should lead to a better understanding of the etiology of CVD. Ultimately, the results of these studies should provide clues for developing new strategies for treatment and prevention of CVD."