One of the most important conclusions from this series of studies is that most of the genes expected, on an a priori basis, to be associated with drug dependence were not those which were most consistently identified in GWAS. Indeed, in analyzing the 96 genes in which clusters of positive SNPs were identified in the Liu et al. (2006) study, almost no monoaminergic system genes are were found, whereas 28% of the genes associated with drug dependence were cell adhesion molecules, much higher than the overall representation of these genes in the genome. It must be noted that another possibility that might influence the sorts of genes in which allelic variation contributes to addiction could be the ability of particular genes to accumulate variation that might impact upon addiction. That is, certain genes may be too important, and consequently variation too deleterious, to accumulate variations that would impact upon addiction phenotypes, even if variation in those genes has the possibility of doing so as demonstrated in KO studies in mice. In this context it is important to note the deleterious effects of DAT KO and VMAT2 KO noted above.
