The PheWAS also provided insight into potentially complex mechanisms of genetic liability to environmental pathways of risk. In addition to indices of socio-economic status (SES), the addiction-rf was correlated with maternal tobacco smoking during pregnancy and ADHD, in line with evidence that effects ascribed to the prenatal environment may also be mediated by the inheritance of risk loci43,44. The addiction-rf PRS was associated with a family history of serious mental illness, which likely represents an amalgam of genetic and environmental vulnerability45. Finally, disability and SES were also associated with polygenic risk, further supporting the association between environmental risk factors and common genetic effects on SUD liability9,41,46
