The heritability of coronary artery disease (CAD) and myocardial infarction (MI) has been unequivocally demonstrated. However, traditional technology, for example based on investigation of candidate genes, or linkage analysis, has failed to elucidate the genetic roots of the Number One killer in society. Cardiogenics will exploit the major advances in genomics to identify risk genes for CAD/MI. The investigators have established large collections of affected individuals with an exceptionally strong genetic signal and subjected these to high-density genome-wide association analyses. These and other components of a multi-step genome-wide based strategy will uncover strong candidate genes (SCG). The implications of SCGs will be tested by the integrated functional genomics programme. Specifically, we will relate variants of SCG to the transcriptomes of monocytes and coronary plaques as well as more complex human phenotypes. Moreover, SCG variants will be further characterised, by small interfering RNA technology in stem cells, at the protein level, and functionally investigated. Ultimately, our globally competitive, integrated programmes spanning from genome-wide mapping to cell biology will determine the physiological roles of genes and proteins implicated in CAD/MI genetics and thus lead to the identification of novel drugable targets.The likelihood that we will achieve our ambitious goals is greatly increased by the fact that we have brought together leading European academic groups, and received substantial financial and logistic support from major national initiatives (WTCCC in the UK and NGFN in Germany), large pan-European projects (MORGAM, BLOODOMICS, EUMORPHIA), and from Europe's premier genome centre, the WTSI. The seamless transfer of inventions to the small-and-medium-sized enterprises (EUROIMMUN and TRIUM) and the pharmaceutical sector will provide the basis of a return on the initial investment'.
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Funding SchemeIP - Integrated Project