The available genome-wide data also permitted us to compare the opioid-related phenotypes with respect to shared genetic risk of relevant behavioral traits. Although there is variability in the effective sample size and therefore statistical power of the phenotypes tested (ODunexposed Neffective=4,728; OEcontrols: Neffective=5,376; ODexposed Neffective=3,038), the PRS results showed an interesting pattern. The risk-tolerance PRS was positively associated with all three phenotypes with the strength of association mostly related to the effective sample size of the target sample. The association between OEcontrols and genetic liability to risk-taking highlights the importance of accounting for the genetic factors related to the individual differences in exposure when examining those contribution to dependence. Such a finding would support the hypothesis that the inclusion of exposed controls can “fine-tune” our ability to separate loci related to generalized risk-taking from those specific to repeated use that lead to opioid dependence. The neuroticism PRS showed positive associations with ODunexposed and ODexposed phenotype comparisons. Although it was non-significant, we observed a negative association of neuroticism PRS with the OEcontrols phenotype. This suggestive negative relationship parallels the rs9291211 result
