During the 1980s and 1990s, genetic research in cardiovascular disease (CVD), as well as other common chronic diseases, has been dominated by single gene linkage and association studies focused on understanding of the genetics of prevalent disease. Rarely have there been studies of the longitudinal predictive value of these genetic variations. Furthermore, few studies have attempted to address the complex and high-dimensional genetic reality that underlies an individual's risk of disease. A crucial next step in CVD genetic research is the evaluation of the contribution of variations in many genes simultaneously, and their interactions with traditional risk factors, to the longitudinal prediction of CVD in individuals and families.