Keller notes that ignoring two-way interactions between the environmental measure and other covariate terms in GxE analyses can generate spurious findings42. Upon addition of these two-way terms, the moderating effect of religious service attendance was diminished by the inclusion of interactions between service attendance frequency and the first ancestral PC and with sex. Interestingly, within the EA analytic sample, PC1 is significantly positively correlated with Jewish religious affiliations (r: 0.39, p < 0.0001) and negatively correlated with Protestant (non-fundamentalist Baptist, Episcopalian, Lutheran, Methodist, Presbyterian) religious affiliations (r: −0.14, p < 0.0001). The influence of ancestral PC1 is likely reflecting both cultural differences regarding cannabis use by ancestral background (i.e., country of origin) within European Americans and differences by religious affiliation in attitudes toward cannabis use demonstrated by previous studies48,51,52. In addition, religious service attendance was a more prominent buffer from CUD among women relative to men, which is supported by previous studies that have shown the inverse associations of religiosity and substance use behavior are greater among women relative to men48,51,52.
