A programme is proposed, by an established European consortium, that will exploit advances in complex trait genetics and functional genomics to discover novel susceptibility genes for coronary artery disease (CAD). The aim is to identify novel proteins and pathways implicated in atherosclerosis and arterial thrombosis in order to define new targets for prevention and treatment and to devise diagnostic tools that identify disease mechanisms in individuals. The PROCARDIS programme has assembled a uniquely large and carefully phenotyped collection of subjects with early CAD: >2600 affected sibling pairs; >1300 two generation 'trios'; > 5000 genetically enriched cases; >5000 matched controls free from CAD. A genome-wide linkage screen has been completed, identifying and replicating a novel locus on chromosome 17; genetic association has already been demonstrated within this, and another, locus. The proposed second phase of PROCARDIS will incorporate: a definitive genome-wide association analysis, substantial new investment in bioinformatics and functional genomics platforms (as will be needed to exploit the linkage and association data), and measurement of novel intermediate phenotypes that will yield biomarkers for CAD risk and quantitative traits for genetic analysis. Additional academic and SME partners have been selected to reinforce the existing consortium, each with unique and complementary expertise, to address the needs of post-genome research. PROCARDIS will integrate a critical mass to attain ambitious and clearly defined objectives; by adopting parallel approaches, the PROCARDIS programme can include 'higher risk' components without endangering the overall outcome. The results will address a priority theme, will give impetus to Europe's competitiveness and will satisfy major societal needs'.
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