Ascertainment models incorporating effects of variable age of onset

In pedigree analysis, nonrandom sampling, or ascertainment through affected persons, occurs commonly, making it necessary to adjust appropriately for the ascertainment procedure in order to secure the correct interpretation of results from genetic analysis. Ascertainment models for dichotomous phenotypes are considered for disorders characterized by variable age of onset, particularly considering those instances where the probability of ascertainment may be influenced by the age of onset of the disorder. For a variety of theoretical and practical reasons, sigmoidal functions appear to be well suited to the modeling of occurrence of a binary event, such as proband status. Relevant ascertainment models incorporating a modified exponential ascertainment function having such a sigmoidal form are described, together with associated modifications to the likelihood for the ascertained pedigree. Alternative parameterizations and methods for obtaining initial estimates are also discussed.