Poor Performance of Bootstrap Confidence Intervals for the Location of a Quantitative Trait Locus

The aim of many genetic studies is to locate the genomic regions (called quantitative trait loci, QTL) that contribute to variation in a quantitative trait (such as body weight). Confidence intervals for the locations of QTL are particularly important for the design of further experiments to identify the gene or genes responsible for the effect. Likelihood support intervals are the most widely used method to obtain confidence intervals for QTL location, but the nonparametric bootstrap has also been recommended. Through extensive computer simulation, we show that bootstrap confidence intervals behave poorly and so should not be used in this context. The profile likelihood (or LOD curve) for QTL location has a tendency to peak at genetic markers, and so the distribution of the maximum-likelihood estimate (MLE) of QTL location has the unusual feature of point masses at genetic markers; this contributes to the poor behavior of the bootstrap. Likelihood support intervals and approximate Bayes credible intervals, on the other hand, are shown to behave appropriately.