A frailty approach for modelling diseases with variable age of onset in families: the NHLBI Family Heart Study.
Stat Med
; 18(12): 1517-28, 1999 Jun 30.
Article
en En
| MEDLINE
| ID: mdl-10398289
ABSTRACT
We use frailty models to analyse the effect of latent genetic and environmental risk factors on hazard functions in nuclear families. The approach expresses latent risk factors (frailties) as functions of the effects of a single major gene and shared familial risk. The latter may result from shared polygenes and/or a common environment. Genetic frailties are modelled using a two-point distribution, and residual frailties (shared environment, polygenes) using a gamma distribution. The two-point distribution follows the laws of Mendelian transmission, under either dominant or recessive gene action. We describe a robust EM approach for the joint estimation of the magnitude of genetic, covariate, gene by covariate interaction effects while allowing residual familial correlation. We illustrate the method on coronary heart disease data from the National Heart, Lung, and Blood Institute Family Heart Study. In addition, a simulation study shows that ignoring possible residual correlation in disease status due to a shared familial environment leads to an overestimate of the relative risk associated with a latent genotype.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Simulación por Computador
/
Estudios Multicéntricos como Asunto
/
Enfermedad Coronaria
/
Modelos Cardiovasculares
Tipo de estudio:
Clinical_trials
/
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Female
/
Humans
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Male
/
Middle aged
País/Región como asunto:
America do norte
Idioma:
En
Revista:
Stat Med
Año:
1999
Tipo del documento:
Article
País de afiliación:
Estados Unidos