To identify genes that could potentially affect other opioid adaptive traits, we also analyzed the number of times that a gene had a haplotype that was associated with any one of the opioid-response traits analyzed; this analysis also evaluated the strength of the association. Of the associated genes, Dcc was the gene that was most strongly associated with this group of opioid adaptive phenotypes (Table 3). Overall, five genes appeared in the top 15 genes identified using both the robustness and combinatorial analysis: Dcc, Rora, Tcf4, Ctif and Lrch1.Table 3 The integrated ranking of genes associated with the opioid adaptive traits GeneScore Dcc 23.55 Sgpp2 22.51 Sgcz 21.51 Gm16724 21.06 Kank1 20.95 Rora 20.73 Myo5b 20.53 Tcf4 20.20 Dpp10 20.07 Ctif 20.01 Lhfpl3 20.00 Pik3c2g 19.95 Erbb4 19.92 L3mbtl4 19.68 Lrch1 19.59The genes most strongly associated with the five opioid adaptive phenotypes under study considered together are listed in the table. These traits include: mechanical OIH (Mech OIH), OIH measured using tail flick data (TF OIH), OIH measured using paw withdrawal testing (Therm OIH), morphine tolerance (Tolerance) and physical dependence (Dependence). Higher scores indicate stronger combined associations with the group of five traits.
