To account for differences in gene-based mapping methods, we further evaluated the intersection of genes that were identified in all four gene-based analyses. The intersection of genes identified by these four methods resulted in 113 genes for Externalizing, and 97 and 4 (101 total) genes for Behavioral Disinhibition and SUDs, respectively (Figure 3a; Supplementary Table 14). We next identified genes that were unique to each factor (i.e. associated with one and not the other two factors) and found 37 unique genes for Externalizing and 21 for Behavioral Disinhibition and 3 for SUDs in the two-factor model (Figure 3b). Of the 37 genes unique Externalizing genes, 30 (81%) have been previously associated with a substance use phenotype (e.g., initiation, consumption, or use disorder),29 including SMIM19, which has been associated with nicotine dependence, and KLHL29, which has been associated with cannabis, nicotine, and alcohol use. Of the three unique SUD genes, PPP6C has been associated with CUD, AUD, and OUD.
