with alcohol use disorder (two-sided test P = 6.84×10−36) and 66.9% with antisocial behavior (two-sided test P = 1.39×10−15) (Extended Data Fig. 3). For the second and third tests, we generated empirical null distributions for the two phenotypes by randomly selecting 250 near-independent (r2 < 0.1) SNPs per each of the 579 SNPs, matched on allele frequency. In the second test, a greater proportion of the 579 SNPs were nominally associated (P < 0.05) with the two phenotypes compared to their empirical null distributions: 124 (21.4% vs. 6.6%) with alcohol use disorder (two-sided P = 1.87×10−31) and 58 (10.5% vs. 4.7%) with antisocial behavior (P = 1.64×10−8). In the third test, the 579 SNPs were jointly more strongly enriched for association with alcohol use disorder (one-sided Mann-Whitney test P = 5.89×10−26) and antisocial behavior (P = 1.10×10−5) compared to their empirical null distributions. Overall, the three exercises consistently suggested that the GWAS of EXT is not spurious overall, and that it is enriched for genetic signal with two phenotypes of central importance to the literature on externalizing. Below, we perform further quasi-replication of the 579 EXT SNPs in an auxiliary polygenic score analyses (also in within-family models).
