Fifth, the addition of rs1229984 in the models attenuated the effect of the PRS, although only modestly for alcohol use. While rs1229984 exerts one of the strongest effect sizes observed for psychiatric and behavioral traits (Edenberg & McClintick, 2018), other loci related to alcohol dependence are expected to have noticeably more modest effects (Walters et al., 2018). In our analyses, the conditional effect of rs1229984 (i.e., R2 for rs1229984 when including PRS in the model) was greater for DSM4AD and DSM5AUDSX (explaining 0.49 – 1.13% of the variance) than the conditional effect of the PRS after adjusting for rs1229984 (0.40 – 0.42% of variance explained). In fact, the addition of PRS to the model had negligible impact on the variance in DSM4AD and DSM5AUDSX already explained by rs1229984, highlighting this variant’s robust effect on problem drinking. In contrast, rs1229984 did not substantially reduce the variance in alcohol use associated with the PRS; rather, the alcohol consumption PRS explained a greater percent of the variance in alcohol use (1.22%) than rs1229984 genotype (0.49%). This suggests that, despite being an aggregate polygenic
