Analyzing the relationship between age at onset and risk to relatives

Correlations in age at onset between relatives affect risk to relatives of a given age. Either an increase or a decrease in risk may be observed for a relative of a proband, according to whether there is a causal relationship between liability to disease and age at onset. Likelihood formulas are given for pairs of relatives under a number of different sampling schemes, and it is shown how data collected from relatives enable maximum-likelihood estimation of parameters of a linear model relating disease liability and age at onset. A genotype-environment extension of this model was fitted to data on age at onset for schizophrenia that were obtained from the National Academy of Sciences-National Research Council Twin Registry. Age at onset is correlated between twins, but this correlation appears to be associated with factors that are separate from those which affect liability to disease. However, even this relatively large sample of twins is too small to draw firm conclusions about any causal relationship between disease liability and onset.