Using survival methods to estimate age-at-onset distributions for genetic diseases with an application to Huntington disease
✍ Scribed by Dr. L. Adrienne Cupples; Norma C. Terrin; Richard H. Myers; Ralph B. D'Agostino; D. C. Rao
- Publisher
- John Wiley and Sons
- Year
- 1989
- Tongue
- English
- Weight
- 724 KB
- Volume
- 6
- Category
- Article
- ISSN
- 0741-0395
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✦ Synopsis
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 lifetable 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 ( k SE) of inheriting the gene for disease among children of a singly affected parent is estimated to be 0.499 2 0.020 and the estimated mean onset age ( 2 SE) is 45.6 2 0.7.