Genes implicated in the neurobiology of social behavior or aggression have also been hypothesized as plausible candidates for conduct disorder related phenotypes. One example is the Arginine Vasopressin Receptor 1A (AVPR1A) gene, which codes for arginine vasopressin receptor 1A (AVPR1A) receptors in the brain and is associated with social behavior (Ebstein et al., 2010; Walum et al., 2012). Of the 21 candidate genes across the serotonin, dopaminergic, adrenergic, and stress response systems that were tested as part the EAGLE Consortium’s GWAS meta-analysis of childhood aggression (Pappa et al., 2015), only AVPR1A had a gene-based P < 0.05 (P = 1.61 × 10–3). Although this approach is intuitively appealing, selecting the relevant genes for social behavior phenotypes is challenging. In a systematic effort to identify relevant genes, Zhang-James and Faraone (2015) used the Online Mendelian Inheritance in Man (OMIM) catalog to identify 86 genes that harbor known rare variants associated with human disorders that have aggressive features. Although these genes await replication, this illustrates a novel use of validated rare, functional variants to guide gene identification efforts for conduct disorder.
