title: A new statistical test for age-of-onset anticipation: application to bipolar disorder.
abstract: The discovery of expanding microsatellite repeat mechanisms for a variety of diseases has spurred renewed interest in testing for genetic anticipation in complex diseases. However, standard statistical methods can be shown to be inappropriate for this purpose. We derive a new statistical test for comparing mean age of onset in parents with mean age of onset in children, based on a random sample of affected parent-child pairs. This test incorporates the right-truncation of the age-of-onset distributions and utilizes age-at-interview information. We illustrate the use of the test by application to bipolar affective disorder data. In this example, the correct p-value is 0.014 whereas the results based on the biased estimates give a p-value of 0.0001 [McInnis et al., 1993]. We also briefly consider the effects of ascertainment bias when parent-child pairs are obtained from samples collected for purposes of linkage analysis.
authors.affiliation: Department of Statistics and Actuarial Science, University of Iowa, Iowa City 52242, USA.
authors.forename: J
authors.initials: J
authors.lastname: Huang
authors.forename: V
authors.initials: V
authors.lastname: Vieland
mesh_terms: D017668:Age of Onset; D015982:Bias; D001714:Bipolar Disorder / Q000235:genetics*; D005260:Female; D006801:Humans; D016013:Likelihood Functions; D008297:Male; D009679:Nuclear Family; D010290:Parents; D018911:Trinucleotide Repeats