JSM 2004 - Toronto

Abstract #300075

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Activity Number: 144
Type: Invited
Date/Time: Monday, August 9, 2004 : 2:00 PM to 3:50 PM
Sponsor: ENAR
Abstract - #300075
Title: The Role of Frailty Models in Genetics
Author(s): Philip Hougaard*+
Companies: H. Lundbeck A/S
Address: Dept. of Biostatistics, DK-2500 Copenhagen Valby, , Denmark
Keywords: survival data ; frailty ; genetics ; multivariate
Abstract:

Usually genetic dependence is evaluated by normal distribution random effects models. Such models are, however, not sensible for survival data. First, censoring requires numerical integration; second, the normal distribution does not fit well to lifetimes; and third, it does not allow the flexibility as the standard semiparametric models. Finally, truncation is difficult. Frailty models are random-effects models designed for censored survival data, with dependence modeled by a factor on the hazard. I will discuss to which extent they can serve the same purpose as normal models. That is, basic questions like what is genotype and phenotype, and complicated questions like how to split variance into components. Both shared frailty and correlated frailty models are considered. Two applications are used. First, survival of like-sex Danish twins born 1870-1930, with both alive by age 6 and follow-up to 1995. Second, recurrent hypoglycemic episodes for diabetic patients according to the ACE gene. Frailty models are well suited to evaluate dependence, but evaluation of genetic variance components is not possible due to lack of a sensible scale, on which the terms act additively.

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