Whole-genome HBCGM was used to analyze the opioid-related traits. We focused on mechanical OIH as the trait of primary interest, and examined the 15 genes whose haplotypic pattern were most strongly associated with this response (Figure 2). The 7 genes that were most strongly associated with this phenotype had haplotype blocks that partitioned the strains in an identical fashion, and therefore generated the same p value. None of the top 15 genes had previously been associated with OIH, as determined by a search of the PubMed database (using the gene name and “opioid-induced hyperalgesia” or “opioid” or “morphine.”) Although these 15 genes all had highly significant statistical correlations with mechanical OIH, it was difficult to determine which was most likely to be a causative genetic factor. Therefore, we assessed the robustness of the mapping results as described in Methods. In brief, we determined which of the mapped genes was most resistant (i.e. robust) to a change in the number of strains used for the genetic mapping. Of note, 13 of the 15 genes that were most robustly associated with OIH,
