Ascertainment adjustment in genetic studies of ordinal traits.

Most genetic studies recruit high risk families and the discoveries are based on non-random selected groups. We must consider the consequences of this ascertainment process in order to apply the results of genetic research to the general population. In previous reports, we developed a latent variable model to assess the familial aggregation and inheritability of ordinal-scaled diseases, and found a major gene component of alcoholism after applying the model to the data from the Yale family study of comorbidity of alcoholism and anxiety (YFSCAA). In this report, we examine the ascertainment effects on parameter estimates and correct potential bias in the latent variable model. The simulation studies for various ascertainment schemes suggest that our ascertainment adjustment is necessary and effective. We also find that the estimated effects are relatively unbiased for the particular ascertainment scheme used in the YFSCAA, which assures the validity of our earlier conclusion.