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Genetics, Vol. 168, 1689-1698, November 2004, Copyright © 2004
doi:10.1534/genetics.103.023903
Mapping Quantitative Trait Loci With Censored Observations
Guoqing Diao, D. Y. Lin1 and Fei Zou
Department of Biostatistics, University of North Carolina, Chapel Hill, North Carolina 27599-7420
1 Corresponding author: Department of Biostatistics, University of North Carolina, 3101E McGavran-Greenberg Hall, CB 7420, Chapel Hill, NC 27599-7420.
E-mail: lin{at}bios.unc.edu
The existing statistical methods for mapping quantitative trait loci (QTL) assume that the phenotype follows a normal distribution and is fully observed. These assumptions may not be satisfied when the phenotype pertains to the survival time or failure time, which has a skewed distribution and is usually subject to censoring due to random loss of follow-up or limited duration of the experiment. In this article, we propose an interval-mapping approach for censored failure time phenotypes. We formulate the effects of QTL on the failure time through parametric proportional hazards models and develop efficient likelihood-based inference procedures. In addition, we show how to assess genome-wide statistical significance. The performance of the proposed methods is evaluated through extensive simulation studies. An application to a mouse cross is provided.
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