SURVIVAL MODELS FOR DEVELOPMENTAL GENETIC DATA - AGE-OF-ONSET OF PUBERTY AND ANTISOCIAL-BEHAVIOR IN TWINS

The use of survival analysis for developmental genetic data is discuss ed. The main requirements for models based on the decomposition of fra ilty distributions into shared and unshared components are outlined fo r the simple case of twins. Extending the earlier work of Clayton, Oak es, and Hougaard, among others, three forms of hazard model are presen ted, all of which can be applied to pedigree data with flexible baseli ne hazards without the use of numerical integration. The first two mod els use an additive decomposition of frailty, with either gamma or pos itive stable law distributed (PSL) components. The third model previou sly described by Hougaard involves a multiplicative PSL decomposition. The models are applied to data on the onset of puberty in male twins and illustrate the importance of correct specification of the baseline hazard for correct inference about genetic effects. The difficulty of assessing model specification using information only on the margins i s also noted. Overall, the new model with additive PSL components appe ared to fit these data best. A second application illustrates the use of a time-varying covariate in examining the impact of puberty on the onset of conduct disorder symptomotology. (C) 1994 Wiley-Liss, Inc.