Recent GWAS have identified several regions containing a set of genes that have pleiotropic effects on many psychiatric disorders and related traits; these genes may be tagging a latent factor (“p-factor”) (42). For example, the largest GWAS of alcohol and smoking, which used over 1 million individuals, performed a multivariate GWAS approach to show that 150 loci were associated with multiple substance use phenotypes; variation at PDE4B and CUL3 were associated with both smoking (initiation, cessation, quantity) and drinks per week. Similarly, CADM2 has been recently associated with alcohol and cannabis use (21, 23, 43). CADM2 is a cell adhesion molecule (CAM) that influences brain wiring and appears to have a role in multiple neuropsychiatric disorders (44). There is now mounting evidence from independent GWAS showing an association between common genetic variants at CADM2 and risky or impulsive behaviors including risk tolerance, automobile speeding propensity, number of sexual partners (45), sensation seeking and drug experimentation (46), cannabis initiation (47), and obesity and body mass index (48–50). CADM2 has also been associated with cognitive phenotypes, including educational attainment (51, 52). We
