It has been pointed out that each of the genetic loci that were identified by analysis of inbred strains [1, 24] accounted for only a small fraction (usually ~5%) of the overall trait variation. This analysis has fueled the concern that murine GWAS will be futile endeavors for most traits of interest, since these studies cannot identify genetic loci with a small phenotypic effect. For example, our simulations indicate that genetic loci must be responsible for at least 15% of the overall trait difference to be reliably identified by HBCGM (80% power) [8]. However, murine genetic studies have systematically under-estimated the percent of phenotypic variance that can be explained by a causative genetic locus (PoPVg) for a number of reasons. First, the PoPVg has previously been calculated from analyses that evaluated a very small number of strains. Only two strains are evaluated in conventional linkage studies, while genomic regions from only 6–8 founder strains are evaluated in linkage analyses using heterogeneous stock [24] or collaborative cross [25] mice. Analysis of a small number of strains does not represent the actual
