Various topics in the area of genetic epidemiology are to be explored. The first topic is the detection of genetic heterogeneity. Different approaches include: (1). Analysis of segregation distributions within sibships, determining the circumstances under which heterogeneity can be detected; examination of the expected and observed number of families with r affected children (r=1,2,...) is proposed. (2). Incorporating environmental variables into the segregation analysis. The segregation parameter can be made to be a function of maternal and/or offspring varibles. One appropriate function is the logistic. (3). Developing and characterizing a genetic heterogeneity likelihood model for pedigrees. Several forms of a disease are assumed to exist in he population (major locus, polygenic, sporadic). The overall likelihood then weights the posterior likelihood of each pedigree for each mode of inheritance with its prior frequency of occurrence. (4). Characterizing a test for linkage when heterogeneity is present as described by Risch and Baron (in press) and determining its power and robustness. The second topic is demographic effects on genetic analysis. First, a maximum likelihood method for morbidity risk estimation with variable age-of-onset is described, and a method for extension to include effects of reduced fertility and increased mortality is given. Determining the effects of differential fertility and mortality on family size distribution in segregation analysis is proposed. The third topic is development of multivariate methodology for te analysis of major loci with pleiotropic effects. The techniques of latent trait analysis are suggested as a solution to this problem. All methods developed are intended for application where appropriate.
