Estimating penetrance from family data using a retrospective likelihood when ascertainment depends on genotype and age of onset. - Archive ouverte HAL Access content directly
Journal Articles Genetic Epidemiology Year : 2004

Estimating penetrance from family data using a retrospective likelihood when ascertainment depends on genotype and age of onset.

(1) , (1)
1

Abstract

In diseases caused by deleterious gene mutations, knowledge of age-specific cumulative risks is necessary for medical management of mutation carriers. When pedigrees are ascertained through several affected persons, ascertainment bias can be corrected by using a retrospective likelihood. This likelihood is a function of the genotypes of pedigree members given their phenotypes and provides unbiased estimates of penetrance without modeling the selection process, provided that selection is independent of genotypes. However, since mutation testing is offered only to relatives of mutation carriers, the genotypes of family members are available only in mutated families and selection does depend on genotype. In the present study, we quantified the bias due to selection on genotype using simulations. We found that this bias depended on the true penetrance value: the lower the penetrance, the higher the bias (risk by age 80 estimated to be 46% for a true penetrance value of 20%). When age of onset is added to the selection criteria, as usually done, we showed that the bias was even higher. We modified the conditioning in the retrospective likelihood, what we call "genotype restricted likelihood" (GRL). Using simulations, we show that this method provided unbiased parameter estimates under all the selection designs considered.
Fichier principal
Vignette du fichier
penetrance_revised.pdf (163.19 Ko) Télécharger le fichier
Origin : Files produced by the author(s)

Dates and versions

inserm-00359199 , version 1 (06-05-2011)

Identifiers

Cite

Jérôme Carayol, Catherine Bonaïti-Pellié. Estimating penetrance from family data using a retrospective likelihood when ascertainment depends on genotype and age of onset.: Estimating penetrance from family data. Genetic Epidemiology, 2004, 27 (2), pp.109-17. ⟨10.1002/gepi.20007⟩. ⟨inserm-00359199⟩
158 View
398 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More