Within a non-Hispanic White sample, this gene set (see Supplement for list of genes) showed an enrichment of associations with a Persistent Externalizing factor beyond a conservative, empirically derived, significance threshold. Importantly, the enrichment effect was more robust for this general factor than for any domain-specific residual factor, and the enrichment signal survived removal of the measure with the highest loading (cannabis, Table 1) in a re-estimated model. The only two residual factors for which some enrichment was detected were alcohol and property crime. These results are consistent with the hypothesis that externalizing behaviors share a substantial degree of genetic etiology (Krueger et al., 2002), and that genetic risks for alcohol use disorders are associated not only with alcohol-related outcomes, but with the broader construct of externalizing behavior. Lastly, we demonstrated that the total variance captured by this narrow set of 104 genes was 2.6%, which is nearly half the variance accounted for by genome-wide polygenic risk approach in another recent study (6%, Salvatore et al., 2015).
