To further dissect the allelic architecture of alcoholism in our two study populations, we re-ran the scoring routines on non-overlapping bins of risk alleles, based either on GWAS P-values or classes of minor allele frequency. For the target samples, we observed significant R2 values for scores representing weakly associated risk alleles, including ones for significance thresholds as permissive as 0.50 ≤ P < 0.55 (OR: 1.05–1.15; R2 = 0.30%; P = 0.027) and 0.55 ≤ P < 0.60 (OR: 1.07–1.26; R2 = 1.42%; P = 0.0012) for EAs and AAs, respectively (Fig. 2a; Table S4). When broken down by frequency, a skew in the R2 distribution towards more common markers is evident (Fig. 2b; Table S5), with a peak at 0.3 ≤ MAF < 0.4 for both population samples (EA: R2 = 0.57%, P = 0.0047; AA: R2 = 2.13%, P = 0.00013), suggesting an important role for highly common variants in the liability of AD if one assumes a robust LD relationship between score alleles and the unknown causal loci.
