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 discussed. The main requirements for models based on the decomposition of frailty distributions into shared and unshared components are outlined for the simple case of twins. Extending the earlier work of Clayton, Oakes, and Hougaard, among others, three forms of hazard model are presented, all of which can be applied to pedigree data with flexible baseline hazards without the use of numerical integration. The first two models use an additive decomposition of frailty, with either gamma or positive stable law distributed (PSL) components. The third model previously 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 is also noted. Overall, the new model with additive PSL components appeared 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. © 1994 Wiley‐Liss, Inc.

[1]  R. Prentice,et al.  Regression analysis of grouped survival data with application to breast cancer data. , 1978, Biometrics.

[2]  A. Pickles,et al.  The outcome of childhood conduct disorder: implications for defining adult personality disorder and conduct disorder , 1992, Psychological Medicine.

[3]  P. Hougaard Survival models for heterogeneous populations derived from stable distributions , 1986 .

[4]  M. Levin On the Causation of Mental Symptoms: An Inquiry into the Psychiatric Application of Hughlings Jackson's Views on the Causation of Nervous Symptoms, with Particular Reference to their Application to Delirium and Schizophrenia , 1936 .

[5]  K. Merikangas,et al.  The use of survival time models with nonproportional hazard functions to investigate age of onset in family studies. , 1986, Journal of chronic diseases.

[6]  P. Hougaard A class of multivanate failure time distributions , 1986 .

[7]  D. Clayton,et al.  Multivariate generalizations of the proportional hazards model , 1985 .

[8]  O. Aalen,et al.  Statistical analysis of repeated events forming renewal processes. , 1991, Statistics in medicine.

[9]  A. Pickles,et al.  The analysis of residence histories and other longitudinal panel data: A continuous time mixed markov renewal model incorporating exogeneous variables , 1983 .

[10]  D G Clayton,et al.  A Monte Carlo method for Bayesian inference in frailty models. , 1991, Biometrics.

[11]  Philip Hougaard,et al.  Measuring the Similarities between the Lifetimes of Adult Danish Twins Born between 1881–1930 , 1992 .

[12]  B. Langholz,et al.  Survival models for familial aggregation of cancer. , 1990, Environmental health perspectives.

[13]  Thomas A. Louis,et al.  Time-Dependent Association Measures for Bivariate Survival Distributions , 1992 .

[14]  L. Eaves,et al.  Estimating genetic parameters of survival distributions: A multifactorial model , 1988, Genetic epidemiology.

[15]  K. Kendler,et al.  Analyzing the relationship between age at onset and risk to relatives. , 1989, American journal of human genetics.

[16]  S. Fischbein Onset of puberty in MX and DZ twins. , 1977, Acta geneticae medicae et gemellologiae.

[17]  K. Kendler,et al.  Age at onset in schizophrenia. A familial perspective. , 1987, Archives of general psychiatry.

[18]  D. Clayton A model for association in bivariate life tables and its application in epidemiological studies of familial tendency in chronic disease incidence , 1978 .