Figure 6). Leveraging the polygenic architecture of the complex traits investigated, in the EUR sample, MaxAlc in MVP showed rg=0.87 with AD in the PGC cohort (p=4.78×10−9) by LDSC. For additional replication, we investigated UK Biobank data regarding nine traits related to alcohol use (Supplementary Table 5). To identify the phenotypes most closely related to MaxAlc, we performed a genetic-correlation analysis and observed the strongest correlation with “Amount of alcohol drunk on a typical drinking day” (rg=0.81, p=5.83×10−40). Significant correlations were also observed with the other traits, including “Frequency of consuming six or more units of alcohol” (rg=0.70, p=2.72×10−30), “Ever been injured or injured someone else through drinking alcohol” (rg=0.84, p=8.56×10−5), and “Ever had known person concerned about, or recommend reduction of, alcohol consumption” (rg=0.64, p=3.79×10−14). Considering the most strongly genetically correlated alcohol-use trait (i.e., “Amount of alcohol drunk on a typical drinking day”), we observed replications (Supplementary Table 4) for chromosome 4 rs1229984 (p=3.77×10−32), chromosome 10 rs1577857 (p=0.027), and chromosome 17 rs77804065 (p=2.67×10−6) and rs61667602 (p=1.25×0−6).
