Most standard QTL mapping procedures apply to populations derived from the cross of two parents. QTL detected from such biparental populations are rarely relevant to breeding programs because of the narrow genetic basis: only two alleles are involved per locus. To improve the generality and applicability of mapping results, QTL should be detected using populations initiated from multiple parents, such as the multiparent advanced generation intercross (MAGIC) populations. The greatest challenges of QTL mapping in MAGIC populations come from multiple founder alleles and control of the genetic background information. We developed a random-model methodology by treating the founder effects of each locus as random effects following a normal distribution with a locus-specific variance. We also fit a polygenic effect to the model to control the genetic background. To improve the statistical power for a scanned marker, we release the marker effect absorbed by the polygene back to the model. In contrast to the fixed-model approach, we estimate and test the variance of each locus and scan the entire genome one locus at a time using likelihood-ratio test statistics. Simulation studies showed that this method can increase statistical power and reduce type I error compared with composite interval mapping (CIM) and multiparent whole-genome average interval mapping (MPWGAIM). We demonstrated the method using a public Arabidopsis thaliana MAGIC population and a mouse MAGIC population.KEYWORDS best linear unbiased prediction; empirical Bayes; mixed model; polygene; restricted maximum likelihood; multiparental populations; Multiparent Advanced Generation Inter-Cross (MAGIC); MPP T HERE is an urgent need to develop and study multiparent advanced generation intercross (MAGIC) populations (Rakshit et al. 2012). Along with nested association mapping populations (Yu et al. 2008), the MAGIC population is called a second-generation mapping resource (Rakshit et al. 2012). Using MAGIC populations to perform QTL mapping was first proposed for mice by Threadgill et al. (2002). Such a population is called the Collaborative Cross (CC) population (Churchill et al. 2004;Collaborative Cross Consortium 2012). Simulation studies showed that an eight-parent CC population with 1000 progenies is capable of increasing mapping resolution to the sub-centimorgan range (Valdar et al. 2006). MAGIC populations in Drosophila melanogaster are called Drosophila Synthetic Population Resources (DSPR) (MacDonald and Long 2007; King et al. 2012a, et al.b). A review of MAGIC populations in crops can be found in Huang et al. (2015). The first plant MAGIC population was developed in Arabidopsis thaliana by Kover et al. (2009). The population will be described later. Subsequently, MAGIC populations have been developed in wheat (Huang et al. 2012;Mackay et al. 2014), rice (Bandillo et al. 2013), and other crop species (Gaur et al. 2012;Pascual et al. 2015;Sannemann et al. 2015). One key difference between MAGIC populations and other multiparent populations is ...