Mixture cure model with an application to interval mapping of quantitative trait loci |
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Authors: | Mengling Liu Wenbin Lu Yongzhao Shao |
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Institution: | (1) Division of Biostatistics, School of Medicine, New York University, 650 First Ave, 526, New York, NY 10016, USA;(2) Department of Statistics, North Carolina State University, Raleigh, NC, USA |
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Abstract: | When censored time-to-event data are used to map quantitative trait loci (QTL), the existence of nonsusceptible subjects entails
extra challenges. If the heterogeneous susceptibility is ignored or inappropriately handled, we may either fail to detect
the responsible genetic factors or find spuriously significant locations. In this article, an interval mapping method based
on parametric mixture cure models is proposed, which takes into consideration of nonsusceptible subjects. The proposed model
can be used to detect the QTL that are responsible for differential susceptibility and/or time-to-event trait distribution.
In particular, we propose a likelihood-based testing procedure with genome-wide significance levels calculated using a resampling
method. The performance of the proposed method and the importance of considering the heterogeneous susceptibility are demonstrated
by simulation studies and an application to survival data from an experiment on mice infected with Listeria monocytogenes. |
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Keywords: | EM algorithm Genome-wide threshold Parametric proportional hazards model QTL mapping Time-to-event data |
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