A comparison of bootstrap methods to construct confidence intervals in QTL mapping

The determination of empirical confidence intervals for the location of quantitative trait loci (QTLs) by interval mapping was investigated using simulation. Confidence intervals were created using a non-parametric (resampling method) and parametric (resimulation method) bootstrap for a backcross population derived from inbred lines. QTLs explaining 1%, 5% and 10% of the phenotypic variance were tested in populations of 200 or 500 individuals. Results from the two methods were compared at all locations along one half of the chromosome. The non-parametric bootstrap produced results close to expectation at all non-marker locations, but confidence intervals when the QTL was located at the marker were conservative. The parametric method performed poorly; results varied from conservative confidence intervals at the location of the marker, to anti-conservative intervals midway between markers. The results were shown to be influenced by a bias in the mapping procedure and by the accumulation of type 1 errors at the location of the markers. The parametric bootstrap is not a suitable method for constructing confidence intervals in QTL mapping. The confidence intervals from the non-parametric bootstrap are accurate and suitable for practical use.