PRS had a greater influence on cannabis ever use and DSM-5 CUDsx among those who less frequently attended religious services as compared to those who more frequently attended services (Fig. 2b). However, in models that also included cross-terms for all variables in the interaction model, no significant moderation effects were observed (Model 2, Table 3). Post hoc step-wise models indicated that the interaction among frequency of service attendance and the PRS was diminished by the inclusion of sex × religious service attendance frequency (however, the PRS by service attendance frequency interaction remained statistically significant, p < 0.037). The inclusion of the ancestral PC1 by religious service attendance frequency interaction significantly reduced the variance explained by this model (p > 0.30). Sensitivity analyses were conducted stratified by age (above and below age 18 years) to determine whether effects differed by age; similar results were observed for those under and over age 18 years. Religious service attendance was unrelated to cannabis use PRS (p > 0.14). However, the first genetic ancestral component (PC1) was positively correlated with Jewish religious affiliations (r: 0.39, p < 0.0001) and negatively correlated with Protestant religious affiliations (r: −0.14, p < 0.0001).