due to the ancestral composition of the discovery cohorts in the Pasman et al. study9. While congruent with what is expected for PRS derived from GWASs with sample sizes and effect sizes similar to those observed in Pasman et al.9, predictive power of the PRS observed in this study was poor or non-significant for CUDsx. Given the reliance of PRS on large, well-powered samples, future studies should re-examine the relations examined in this study with larger studies that will soon be available to the research community. In addition, GWAS that specifically examine problematic cannabis use may be needed to achieve predictive utility for CUD. Finally, these findings may not be generalizable to individuals of other ancestral backgrounds as seen in our AA cohort (Supplementary Table 2). While Supplementary Table 2 shows the prediction of cannabis use and CUDsx in COGA’s participants of AA, we note the limitations of applying EA-derived summary statistics to participants of AA. Large discovery GWAS in non-Europeans could be foundational in bridging the disparity in PRS research that is heavily weighted toward European populations even though negative consequences of addictions disproportionately impact those from other ancestral backgrounds53.
