Coronary artery disease (CAD) is the single leading cause of death in the US. CAD is a complex disease with clear genetic and environmental risk factors. Early onset (premature) coronary artery disease (EOCAD), defined as age of onset less than 50 years of age, is known to have a particularly strong genetic component. However, the actual genes leading to this increased risk and to a basic understanding of CAD remain obscure. We propose to perform a gene mapping study using microsatellite markers in 438 families with multiple members with CAD. We hypothesize that affected individuals, particularly individuals with an early age of onset, have an underlying genetic susceptibility to development of CAD. We will use a comprehensive strategy comprising fine mapping, candidate gene analysis, and family-based association studies using microsatellite goals of the CEGS. First, it provides an independent approach to identify candidate genes for population-based association studies, one based on the genome location of susceptibility alleles in high-risk families, and not on biological assumptions about underlying physiology. Second, it provides a novel approach for the selection of genes for """"""""custom"""""""" printed arrays for expression analyses, again, one that is based on the genome location of susceptibility alleles, and not on biological biases.
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