Interval mapping methods for detecting QTL affecting survival and time-to-event phenotypes.
Quantitative trait loci (QTL) are usually searched for using classical interval mapping methods which assume that the trait of interest follows a normal distribution. However, these methods cannot take into account features of most survival data such as a non-normal distribution and the presence of censored data. We propose two new QTL detection approaches which allow the consideration of censored data. One interval mapping method uses a Weibull model (W), which is popular in parametrical modelling of survival traits, and the other uses a Cox model (C), which avoids making any assumption on the trait distribution. Data were simulated following the structure of a published experiment. Using simulated data, we compare W, C and a classical interval mapping method using a Gaussian model on uncensored data (G) or on all data (G'=censored data analysed as though records were uncensored). An adequate mathematical transformation was used for all parametric methods (G, G' and W). When data were not censored, the four methods gave similar results. However, when some data were censored, the power of QTL detection and accuracy of QTL location and of estimation of QTL effects for G decreased considerably with censoring, particularly when censoring was at a fixed date. This decrease with censoring was observed also with G', but it was less severe. Censoring had a negligible effect on results obtained with the W and C methods.
Moreno
C R
CR
INRA, Station d'Amélioration Génétique des Animaux, BP27, 31326 Castanet-Tolosan Cedex, France. moreno@toulouse.inra.fr
Elsen
J M
JM
Le Roy
P
P
Ducrocq
V
V
D000818:Animals; D002874:Chromosome Mapping / Q000379:methods*; D003198:Computer Simulation; D051379:Mice / Q000235:genetics; D008957:Models, Genetic; D016011:Normal Distribution; D010641:Phenotype; D016016:Proportional Hazards Models; D040641:Quantitative Trait Loci; D012486:Salmonella typhimurium / Q000472:pathogenicity