A series of theoretical studies are proposed to develop and evaluate statistical approaches to resolving alternative hypotheses about the genetic and environmental determinants of aging and age-related diseases. Four approaches to the genetic analysis of age-related phenomena will be investigated: extension of time series models to incorporate genetic and environmental effects; analysis of the extent and cause of correlation between disease liability and age of onset; the statistical-genetic consequences of age-related degeneration of homeostatic control of gene regulation and sensitivity to the environment the incorporation of genetic and environmental heterogeneity into survival analysis models or age-dependent events. Computer programs will be developed to stimulate and analyze kinship data in each of the major areas of interest with the principal goal of deciding how far quantitative genetic studies of age related phenomena can elucidate the genetic and environmental processes underlying different aspects of the aging process. The resolving power of different strategies will be explored, and the effects of bias and errors of inference assessed. Appropriate methods will be applied to illustrative data from a large longitudinal study of cardiovascular risk in twins and their parents (N=330 families) and to a study of common age-dependent disease and disease-related risk factors in two large studies of twins and their relatives (N=5000 pairs and N=14000 twins plus 7000 relatives, approximately). By the end of the five year project the theoretical and computational tools available to genetic research into aging should be significantly enhanced.
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