This is one of the first GWAS to test for the association of overall substance dependence phenotypes, defined both categorically (dependence diagnosis for alcohol, cannabis, cocaine or opioids; ANYDEP) and quantitatively (factor analysis of the 7 DSM-IV dependence criteria, across alcohol, cannabis, cocaine and opioids; QUANTDEP). This approach implicitly tested the hypothesis that there are genes with pleiotropic effects contributing to dependence on alcohol, cannabis, cocaine and opioids. Using these multi-substance phenotypes, we detected genome-wide significant results with SNPs in two different genes. This finding is consistent with an extensive twin literature that provides demonstrable support for common genetic liability underlying addiction to multiple substances (Kendler et al., 2003; Tsuang et al., 2001). Furthermore, a previous study in a slightly different COGA sample demonstrated aggregation of drug dependence in relatives of alcohol-dependent probands, even after controlling for comorbidity in the probands (Nurnberger et al., 2004).
