We propose to expand the research focus of the Center for Cardiovascular Disease Prevention by hiring an independent faculty recruit trained in human genetics, who will have a joint appointment in the Departments of Medicine and Molecular and Human Genetics at Baylor College of Medicine, to perform research in two main areas that are directly relevant to improving prevention of coronary heart disease (CHD). He/she will establish effective tools for assessment and stratification of CHD risk based on genetic variation, mainly single nucleotide polymorphisms (SNPs). He/she will fully characterize known and novel genes and genomic regions that affect high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), and CHD in a special subpopulation consisting of individuals in the upper and lower extremes for TG or HDL-C. The overall strategy of this approach has clear therapeutic goals: 1. Better accuracy of risk prediction and classification, based on the individual's genetic information, thus enabling more appropriate preventive treatment. 2. Identification of genes and genomic regions associated with HDL-C, TG, CHD risk, and response to commonly used drugs to treat lipid disorders. Achieving these goals will develop and extend inter- and intra-institutional collaborations that are already ongoing. Data from the largest prospective cohort studies in the United States-the Atherosclerosis Risk in Communities (ARIC), Candidate Gene Association Resource (CARE), and Cohorts for Heart and Aging Research in Genome Epidemiology (CHARGE) studies-will be analyzed by the recruit in close collaboration with the Department of Molecular and Human Genetics at Baylor College of Medicine and the Human Genetics Center at The University of Texas School of Public Health to identify SNPs associated with low HDL-C, high TG, and CHD risk. Genes found by the association studies will be sequenced by the Human Genome Sequencing Center at Baylor College of Medicine in a population of patients with low HDL-C and high TG participating in a double-blind study of statin and fibrate therapy, to examine the association of sequence variations in the genes with HDL-C and TG levels, and to determine the influence of these genes on lipid changes in response to commonly used drugs. Genetic information will therefore be applied in an effort to refine CHD risk assessment and to improve risk reduction through personalized preventive therapy. Cardiovascular disease remains the leading cause of death and medical expenses in the United States. Prevention of cardiovascular disease can be improved by using recent genetic discoveries to identify who is at risk of developing a heart attack and by improved understanding of the genes that control the levels of fats (triglycerides and HDL ["good"] cholesterol) in blood.