title: Using survival methods to estimate age-at-onset distributions for genetic diseases with an application to Huntington disease.
abstract: Two important considerations in genetic disease are the risk of inheriting the gene for a disease and the age-at-onset distribution among those inheriting it. This paper describes the use of survival data analytic methods to estimate these entities. When a sample consists of children and/or siblings of affected individuals, standard life-table methods such as Kaplan-Meier techniques can be applied. The desired estimators are functions of the Kaplan-Meier estimator and their properties are derived using the invariance principle and delta methods. A discussion of the underlying assumptions and estimators of standard errors and mean onset age are given. In an application to Huntington disease, the risk (+/- SE) of inheriting the gene for disease among children of a singly affected parent is estimated to be 0.499 +/- 0.020 and the estimated mean onset age (+/- SE) is 45.6 +/- 0.7.
authors.affiliation: Epidemiology and Biostatistics Section, School of Public Health, Boston University School of Medicine, Massachusetts.
authors.forename: L A
authors.initials: LA
authors.lastname: Cupples
authors.forename: N C
authors.initials: NC
authors.lastname: Terrin
authors.forename: R H
authors.initials: RH
authors.lastname: Myers
authors.forename: R B
authors.initials: RB
authors.lastname: D'Agostino
mesh_terms: D000206:Actuarial Analysis; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D002648:Child; D002675:Child, Preschool; D004198:Disease Susceptibility; D006580:Genetic Carrier Screening; D006801:Humans; D006816:Huntington Disease / Q000235:genetics / Q000401:mortality*; D008875:Middle Aged; D012307:Risk Factors