Multiple quantitative trait loci Haseman-Elston regression using all markers on the entire genome

The Haseman-Elston (HE) regression, developed in the 1970s, remains in common use to detect genetic linkage between a quantitative trait and a genetic marker. Although the technique has been improved in a number of ways, it predicts a high rate of false positive quantitative trait locus (QTL) because it is based on a single-QTL model. We have extended the origin HE regression to multi-QTL HE (MQHE) regression, so that all markers across the entire genome can be exploited simultaneously. The parameters have been estimated by the penalized maximum likelihood method, and several response variables for phenotypic difference have been compared in order to optimize the procedure. The method has been tested by simulation in a pedigree population of maize inbred lines of known ancestry. These simulations show that the trait product is the optimal response variable for phenotypic difference. The false positive rate produced by the MQHE regression is substantially lower than that generated by either variance component analysis or the origin HE regression. The MQHE regression, with the trait product as the response variable, represents a significant improvement on existing methods for QTL mapping in a set of inbred lines (or cultivars) of known ancestry.