Testing for age-at-onset anticipation with affected parent-child pairs.

The tendency for the onset of a genetic disease to occur at progressively earlier ages or with progressively greater severity in successive generations is known as anticipation. Following the discovery of trinucleotide repeat expansion as a plausible genetic mechanism for anticipation, interest in testing for anticipation has increased. Studies of anticipation can be biased when parents with late onset or children with early onset are preferentially ascertained. This paper presents a nonparametric approach to testing for age-at-onset anticipation that adjusts for such preferential ascertainment. The approach is illustrated through application to data on panic disorder.