We conducted proxy-phenotype69 and quasi-replication70 analyses by investigating the 579 EXT SNPs for association in two independent, second-stage GWAS on (1) alcohol use disorder (N = 202,004, rg = 0.52) and (2) antisocial behavior (N = 32,574, rg = 0.69) (Supplementary Information section 4) (Supplementary Tables 11–12). For SNPs missing from the second-stage GWAS, we analyzed proxy SNPs (r2 > 0.8). Significant proxy-phenotype associations were evaluated for Bonferroni-corrected significance (two-sided test P < 0.05/579). For the quasi-replication, we generated empirical null distributions for the second-stage GWAS by randomly selecting 250 near-independent (r2 < 0.1) SNPs matched on MAF (± 1 percentage point) for each of the 579 SNPs. The quasi-replication included three steps: (1) a binomial test of sign concordance to test whether the direction of effect of the SNPs were in greater concordance between the externalizing GWAS and each of the second-stage GWAS compared to what would be expected by chance (H0 = 0.5); (2) a binomial test of whether a greater proportion of the SNPs were nominally significant (two-sided P < 0.05) in the second-stage GWAS compared to
