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New score tests for age-at-onset linkage analysis in general pedigrees.
Callegaro, Andrea; Uh, Hae-Won; Helmer, Quinta; Houwing-Duistermaat, Jeanine J.
Afiliación
  • Callegaro A; Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, The Netherlands Medical Center, PO Box 9600, 2300RC Leiden, The Netherlands. a.callegaro@lumc.nl.
BMC Proc ; 3 Suppl 7: S97, 2009 Dec 15.
Article en En | MEDLINE | ID: mdl-20018094
Our aim is to develop methods for mapping genes related to age at onset in general pedigrees. We propose two score tests, one derived from a gamma frailty model with pairwise likelihood and one derived from a log-normal frailty model with approximated likelihood around the null random effect. The score statistics are weighted nonparametric linkage statistics, with weights depending on the age at onset. These tests are correct under the null hypothesis irrespective of the weight used. They are simple, robust, computationally fast, and can be applied to large, complex pedigrees. We apply these methods to simulated data and to the Genetic Analysis Workshop 16 Framingham Heart Study data set. We investigate the time to the first of three events: hard coronary heart disease, diabetes, or death from any cause. We use a two-step procedure. In the first step, we estimate the population parameters under the null hypothesis of no linkage. In the second step, we apply the score tests, using the population parameters estimated in the first step.

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: BMC Proc Año: 2009 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: BMC Proc Año: 2009 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Reino Unido