a strong selection bias toward strains analyzed in previous studies, which may not be relevant for the current phenotype. Analysis of a small number of strains with a restricted phenotypic range will produce a reduced estimate of the genetic effect on a trait value. In addition, the use of marker SNPs to represent the genetic pattern in murine GWAS also reduces the PoPVg estimate. The underlying haplotype structure among inbred mouse strains is ignored in a conventional GWAS that uses selected marker SNPs. When a small number of strains are analyzed, there are many cases where a marker SNP can have very high LD with a causative SNP, but the marker and causative SNP alleles will produce different GWAS results; and the marker SNP will provide a reduced estimate of the PoPVg (Box 1). Even when the marker and causative SNPs have significant LD (r2=0.8), the use of the marker SNP will reduce the calculated PoPVg by 20% relative to the causative SNP (see supplement).
