Modeling DNA Diversity in Reverse Cholesterol Transport

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DESCRIPTION (provided by applicant): Component 3, C. Sing, PI, is an integral part of this Collaborative Research Project grant entitled Modeling DNA Diversity in Reverse Cholesterol Transport involving two other components: population based genomics and DNA genotyping, (Component 1, E. Boerwinkle, PI) and population genetic analysis (Component 2, A. Clark, PI). Although there is a division of labor among components for practical and institutional purposes, the co-investigators and consultants engaged in this project will work as a team to develop resources to address one of the most complex and challenging problems in medicine, how is DNA sequence variation related to variation in human health in the population at large? Component 3 will develop models and test hypotheses about the relationship between DNA sequence variation (identified by Component I and genotyped in samples from the population at large) and variation in measures of health using reverse cholesterol transport (RCT) as the intermediate biological link between the genome and risk to cardiovascular health in the population at large. To accomplish this goal we will utilize information about population structure and genome organization established by Component 2 to: 1) develop new analytical tools (combinatorial partitioning, Bayesian methods, neural networks, etc.) for predicting interindividual variation in risk of cardiovascular disease using DNA sequence variation and 2) identify the variable DNA sites in 62 candidate genes that predict interindividual variation in measures of RCT in population-based samples that are representative of 2007 African-Americans and 2139 European-Americans at baseline and at each of four follow-up times.