Importantly, PRS derived from the unrelated EU GWAS showed much weaker prediction (maximum R2 = 0.37%, p = 0.01; Supplementary Figure S10D) in the COGA AAfGWAS than the ancestrally-matched AA GWAS-based PRS despite the much smaller discovery sample for AA. In addition, the AD PRS also still yielded significant variance explained after controlling for other genetic factors. Prediction of CAGE scores in GS remained significant and showed minimal attenuation (R2 = 0.29%, p = 1.0E-5) after conditioning on PRS for alcohol consumption derived from UK Biobank results17. In COGA AAfGWAS, the AA PRS derived from our study continued to predict 1.6% of the variance in alcohol dependence after inclusion of rs2066702 genotype as a covariate, indicating independent polygenic effects beyond the lead ADH1B variant (Supplementary Information A14).
