who reported not using opioids illicitly were unassessed for medical exposure). Future large opioid-informative datasets will be needed to determine whether illicit and licit opioid exposure have distinct effects on the molecular basis of opioid dependence. Finally, while the phenome-wide investigation in the UK Biobank provides encouraging support for the plausibility of our findings, it may reflect complex pleiotropic effects of these variants on multiple traits, including an unmeasured third variable. Replication of these association signals with opioid dependence and exposure phenotypes will be required.
