A method for simulating familial disease data with variable age at onset and genetic and environmental effects

Abstract

The field of genetic epidemiology is growing rapidly with the realization that many important diseases are influenced by both genetic and environmental factors. For this reason, pedigree data are becoming increasingly valuable as a means of studying patterns of disease occurrence. Analysis of pedigree data is complicated by the lack of independence among family members and by the non-random sampling schemes used to ascertain families. An additional complicating factor is the variability in age at disease onset from one person to another. In developing statistical methods for analysing pedigree data, analytic results are often intractable, making simulation studies imperative for assessing the performance of proposed methods and estimators. In this paper, an algorithm is presented for simulating disease data in pedigrees, incorporating variable age at onset and genetic and environmental effects. Computational formulas are developed in the context of a proportional hazards model and assuming single ascertainment of families, but the methods can be easily generalized to alternative models. The algorithm is computationally efficient, making multi-dataset simulation studies feasible. Numerical examples are provided to demonstrate the methods.