Estimating age-of-onset distributions for disorders with variable onset.

A necessary item of information in many genetic analysis of complex disorders with late onset is the cumulative probability of onset by a given age. The effect of sample design upon the estimation of age-of-onset probability distribution parameters is discussed. Mathematical descriptions of several common sample designs used to estimate the distribution parameters are developed here. Failure to describe the sample space adequately can lead to erroneous genetic analyses because the cumulative probability of onset is incorrectly estimated. In genetic counseling, the errors would usually result in an underestimate of the true risk.