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Publication : Interval mapping of quantitative trait loci for time-to-event data with the proportional hazards mixture cure model.

First Author  Liu M Year  2006
Journal  Biometrics Volume  62
Issue  4 Pages  1053-61
PubMed ID  17156279 Mgi Jnum  J:118315
Mgi Id  MGI:3699389 Doi  10.1111/j.1541-0420.2006.00585.x
Citation  Liu M, et al. (2006) Interval mapping of quantitative trait loci for time-to-event data with the proportional hazards mixture cure model. Biometrics 62(4):1053-61
abstractText  Interval mapping using normal mixture models has been an important tool for analyzing quantitative traits in experimental organisms. When the primary phenotype is time-to-event, it is natural to use survival models such as Cox's proportional hazards model instead of normal mixtures to model the phenotype distribution. An extra challenge for modeling time-to-event data is that the underlying population may consist of susceptible and nonsusceptible subjects. In this article, we propose a semiparametric proportional hazards mixture cure model which allows missing covariates. We discuss applications to quantitative trait loci (QTL) mapping when the primary trait is time-to-event from a population of mixed susceptibility. This model can be used to characterize QTL effects on both susceptibility and time-to-event distribution, and to estimate QTL location. The model can naturally incorporate covariate effects of other risk factors. Maximum likelihood estimates for the parameters in the model as well as their corresponding variance estimates can be obtained numerically using an EM-type algorithm. The proposed methods are assessed by simulations under practical settings and illustrated using a real data set containing survival times of mice after infection with Listeria monocytogenes. An extension to multiple intervals is also discussed.
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