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Epistatic interactions among quantitative trait loci (QTL) contribute substantially to the variation in complex traits. The main objectives of this study were to (i) compare three- vs. four-step genome scans to identify three-way epistatic interactions among QTL belonging to a metabolic pathway, (ii) investigate by computer simulations the power and proportion of false positives (PFP) for detecting three-way interactions among QTL in recombinant inbred line (RIL) populations derived from a nested mating design, and (iii) compare these estimates to those obtained for detecting three-way interactions among QTL in RIL populations derived from diallel and different partial diallel mating designs. The single-nucleotide polymorphism haplotype data of B73 and 25 diverse maize inbreds were used to simulate the production of various RIL populations. Compared to the three-step genome scan, the power to detect three-way interactions was higher with the four-step genome scan. Higher power to detect three-way interactions was observed for RILs derived from optimally allocated distance-based designs than from nested designs or diallel designs. The power and PFP to detect three-way interactions using a nested design with 5000 RILs were for both the 4-QTL and the 12-QTL scenario of a magnitude that seems promising for their identification.

Power to Detect Higher-Order Epistatic Interactions in a Metabolic Pathway Using a New Mapping Strategy