The sample used in the present study was originally recruited as part of a case–control GWAS of alcohol dependence. To check that our results were not simply driven by the phenotypic association between AAB and alcohol dependence, we examined whether the genome-wide significant gene to emerge from our analysis of AAB remained at least nominally significant after statistically controlling for DSM-IV alcohol dependence case–control status using a gene-based test. We also conducted a series of post hoc gene-based pleiotropy analyses to examine whether the genome-wide significant gene to emerge from our analysis showed evidence for association across a broader range of genetically correlated externalizing phenotypes.18 To pursue this, we examined association between our gene of interest and DSM-IV criterion counts for four major drug classes: alcohol dependence, cannabis dependence, cocaine dependence and opioid dependence. Because these were separate analyses of correlated phenotypes, a Bonferroni correction would be too stringent. We therefore used a nominal P-value cutoff of P<0.05 as evidence for association.
