We identified 708 loci in the single factor Externalizing model, in which SUDs were modeled as part of the externalizing spectrum (Supplementary Table 1a). In the two-factor model, we identified 631 and 48 genomic risk loci (679 total) for the Behavioral Disinhibition and SUD factors, respectively (Figure 2; Supplementary Table 4; see Supplementary Text for additional details). Of the 708 Externalizing loci and their correlates within LD regions (r2 > .1), 187 (26%) were not identified in the previous Externalizing17 or Addiction Risk8 GWAS and 403 (57%) were not previously associated with a substance use trait in the GWAS literature (as reported in the NHGRI-EBI GWAS Catalog29 version e114_r2025-06-27). Novel variants include rs11692435 mapped to ACTR1B, which is involved in a variety of cellular functions and has been previously implicated in alcoholic gastritis, alcohol consumption, and smoking initiation and rs10145520, mapped to RAB2B, which is involved in GTP-binding and has been previously implicated in smoking initiation and educational attainment.
