Research on the polygenic structure of psychiatric disorders is advancing rapidly through the development of polygenic scores (PSs) derived from genome-wide association studies. PSs are summary measures that weight single nucleotide polymorphism (SNPs) from across the genome to provide a measured index of the genetic propensity for a given disorder. Salvatore and colleagues (Salvatore et al., 2015) recently developed an externalizing polygenic score in adults with alcohol dependence and showed that it explained 6% of the variance in externalizing disorders (alcohol/substance use disorders, antisocial behavior) and 2–7% of the variance in other disinhibited phenotypes (e.g., impulsiveness). Building on these findings, we recently replicated the association between the polygenic score and externalizing symptoms in trauma-exposed veterans and found that the polygenic score predicted impaired performance on inhibitory control tasks (Sadeh et al., 2016). Thus, initial validation studies find reliable polygenic associations with externalizing phenotypes and illustrate the promise of this approach for identifying heritable neural mechanisms associated with genetic predispositions for externalizing. An important next step in this line of research is to examine the neurobiological correlates of the externalizing PS.
