There are multiple approaches, both phenotypic and genetic, to capture the commonality underlying alcohol and substance use disorders and the present study utilizes two straightforward phenotypic approaches. We opted for simple dependence-based phenotypic traits as they lend themselves to replication and future meta-analysis. First, we utilized a binary phenotype, with affection status defined as meeting dependence criteria for at least one substance (alcohol, cannabis, cocaine or opioids), termed ANYDEP. Second, we used factor analysis to combine dependence criteria across substances into a continuous quantitative trait representing vulnerability to multiple substance dependence, termed QUANTDEP. This quantitative measure is heritable (approx. 60%) (Palmer et al., 2012) and has previously been used in genomic studies (Yang et al., 2012), the most recent of which utilized a similar expanded factorial measure of behavioral disinhibition (including alcohol, nicotine, cannabis and other illicit drug use disorders) to conduct genomewide association and rare nonsynonymous variant analyses (McGue et al., 2013; Vrieze et al., 2013a). These studies did not identify any single common or rare variant at a genomewide significant level; however, the authors reported that 84% of
