Two recent large-scale studies used genomic SEM to examine the genetic architecture of externalizing phenotypes (N = 1 373 240)11 and SUDs (N = 1 019 521),20 respectively. Both identified a single, underlying latent factor that captured the majority of the variance in their indicators. A GWAS of liability to externalizing, operationalized as a latent factor indicated by ADHD, problematic alcohol use, cannabis initiation, smoking initiation, age at first sexual intercourse, number of sexual partners and general risk tolerance, identified 579 conditionally independent loci that largely operated through the latent factor.11 A GWAS of liability to addiction, indexed by problematic alcohol use, problematic tobacco use, cannabis use disorder and opioid use disorder, identified 19 independent loci.21
