Genetic and epidemiologic investigations of the common chronic diseases require a careful combination of elements at several levels, including: study design, ascertainment of individuals, collection of historical and laboratory information, and statistical analysis. As a result of this and the variety of measures which are obtained, such studies are necessarily multidisciplinary. The degree to which all elements complement each other determines in large measure the success of the investigation. The purpose of this Research Career Development Award is to provide an opportunity for welding the analytical approaches of genetics and epidemiology of chronic disease, with current understanding of their underlying biology and sampling designs. In particular, the aims relate to diabetes and gallbladder disease among Mexican Americans of South Texas where these diseases are known to be elevated several-fold over that observed in the United States Population at large. In addition to overt disease and its manifestations, focus is on concomitants of change and lipid and lipoprotein metabolism. Aims include assessing the genetic and environmental sources of the population and familial aggregation of diabetes, gallbladder disease, obesity, and hypertension and lipoprotein measures (including quantitative determinations of apolipoproteins A-I, A-II, B, C-II, C-III, and E). The data to be analyzed is comprised of a sample of 1,509 individuals distributed in some 150 families ascertained through a diabetic; 1,000 random individuals representative of Starr County, Texas; and 1,500 individuals distributed in 100 families ascertained through an individual having gallbladder disease. The sources of coaggregation of these diseases will also be assessed by explicitly modeling the effects that lead to their association. Further, this project will permit assessment of the role of molecular variation at the DNA level (through determination of apolipoprotein restriction fragment length polymorphisms) on the population and familial distribution of proteins and diseases. Finally, the studies above are providing repeated measurements on a subsample so that it is possible to examine these diseases as processes rather than endpoints and to determine the concomitants of change in disease status or severity. The obtaining of a Career Development Award would enhance the ability to achieve these aims by providing an opportunity for further training and interaction with colleagues at a variety of levels, thereby improving the analytical perspective to the common diseases.