JSM 2005 - Toronto

Abstract #303693

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Activity Number: 95
Type: Topic Contributed
Date/Time: Monday, August 8, 2005 : 8:30 AM to 10:20 AM
Sponsor: Biometrics Section
Abstract - #303693
Title: Mapping Quantitative Trait Loci with Time-to-eEvent Data from a Population of Mixed Susceptibility
Author(s): Mengling Liu*+ and Wenbin Lu and Yongzhao Shao
Companies: New York University and North Carolina State University and New York University
Address: School of Medicine, New York, NY, 10016,
Keywords: EM algorithm ; Interval mapping ; Mixture cure model ; Proportional hazards model ; Time-to-event
Abstract:

When quantitative trait loci (QTL) with a time-to-event phenotype are mapped, the latent population heterogeneous susceptibility produces new challenges. The distribution of the time-to-event phenotype usually has a spike because of the existence of a nonsusceptible subpopulation. If we simply ignore the heterogeneous susceptibility or inappropriately handle the nonsusceptible subjects, we may be unable to detect the true genetic effects and find spurious significance at locations with low genotypic information. In this article, we propose a parametric mixture cure model for interval mapping of the QTL that can characterize the genetic effects on the susceptibility and/or the distribution of event times for susceptible subjects. We propose a likelihood ratio-based testing procedure with the genome-wide significance level obtained by a resampling method. We demonstrate the performance of proposed method and the importance of considering the heterogeneous susceptibility by simulation studies and an application to survival data from an experiment on mice infected with Listeria monocytogenes.

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Revised March 2005