Mapping quantitative trait loci with censored observations

Genetics. 2004 Nov;168(3):1689-98. doi: 10.1534/genetics.103.023903.

Abstract

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.

MeSH terms

  • Chromosome Mapping*
  • Computer Simulation
  • Models, Genetic
  • Quantitative Trait Loci*