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Activity Number: 661
Type: Invited
Date/Time: Thursday, August 13, 2015 : 10:30 AM to 12:20 PM
Sponsor: Biometrics Section
Abstract #314461
Title: A Weighted Method for Genetic Association of Survival Data in Selected Families
Author(s): Jeanine Houwing-Duistermaat* and Mar Rodriguez Girondo
Companies: Leiden University Medical Center and Leiden University Medical Center
Keywords: shared frailty ; human longevity ; families ; ascertainment ; delayed entry ; survival
Abstract:

Limited attention has been paid to the analysis of clustered survival data subject to delayed entry. The available methods are not applicable to the general situation of clusters for which not all members are observed. This is typically the case for family studies. Our work is motivated by the Leiden Longevity study comprising 420 sibships with at least two nonagenarian siblings who are alive and willing to participate. Genome wide SNP arrays and ten years of follow up are available; 13% is still alive, maximum observed age is 107 years. The original family sizes vary from 2 to 11, while observed sizes vary from 2 to 5 siblings. To obtain unbiased parameter estimates, we propose a weighted shared frailty model. The weights represent the probability for the family to be in the sample. They depend on the original family size and on the probability to survive until entry time. By means of simulations we will compare the performance of our method and the two existing approaches. We estimated the effect of the APOE E2 allele on survival using data from the Leiden Longevity Study. The estimates of the log hazard ratio was -0.256 and of the variance of the frailty was 0.289.


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