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A frailty approach for modelling diseases with variable age of onset in families: the NHLBI family heart study

✍ Scribed by Kimberly D. Siegmund; Alexandre A. Todorov; Michael A. Province

Publisher: John Wiley and Sons
Year: 1999
Tongue: English
Weight: 120 KB
Volume: 18
Category: Article
ISSN: 0277-6715
DOI: 10.1002/(sici)1097-0258(19990630)18:12<1517::aid-sim132>3.0.co;2-4

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✦ Synopsis

We use frailty models to analyse the e!ect of latent genetic and environmental risk factors on hazard functions in nuclear families. The approach expresses latent risk factors (frailties) as functions of the e!ects 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 frailities (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 e!ects 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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