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

The tendency for the onset of a genetic disease to occur at progressively e arlier ages or with progressively greater severity in successive generation s is known as anticipation. Following the discovery of trinucleotide repeat expansion as a plausible genetic mechanism for anticipation, interest in t esting for anticipation has increased. Studies of anticipation can be biase d when parents with late onset or children with early onset are preferentia lly ascertained. This paper presents a nonparametric approach to testing fo r age-at-onset anticipation that adjusts fur such preferential ascertainmen t. The approach is illustrated through application to data on panic disorde r.