Treatment of the X chromosome in mapping multiple quantitative trait loci

ABSTRACT Statistical methods to map quantitative trait loci (QTL) often neglect the X chromosome and may focus exclusively on autosomal loci. But the X chromosome often requires special treatment: sex and cross-direction covariates may need to be included to avoid spurious evidence of linkage, and the X chromosome may require a separate significance threshold. In multiple-QTL analyses, including the consideration of epistatic interactions, the X chromosome also requires special care and consideration. We extend a penalized likelihood method for multiple-QTL model selection, to appropriately handle the X chromosome. We examine its performance in simulation and by application to a large eQTL data set. The method has been implemented in the package R/qtl.