chromosome 10 (rs1409568)7, which the authors show may have a role as an enhancer in addiction-relevant brain regions, such as the dorsolateral prefrontal cortex and the angular and cingulate gyri. Another recent GWAS of adults in Denmark and Iceland (iPSYCH) implicated a single-nucleotide polymorphism (SNP; rs56372821) that is a strong expression quantitative trait locus for CHRNA2 and that CHRNA2 expression in cerebellum is associated with CUD8. Gene expression profiles in the Allan Brain Atlas (http://www.brain-map.org/), which showed that, of all the genes evaluated (58,692 probes analyzed), cannabinoid receptor 1 gene (CNR1) demonstrated the strongest negative correlation with CHRNA2 expression, led the authors to suggest the possibility of a biological interaction between the endocannabinoid system and alpha-2 subunit containing nicotinic acetylcholine receptor. Notably, there was no evidence of association of these previously identified cannabis risk variants with CUD in the iPSYCH study8. This might be due to different phenotype definitions among the studies: the Yale-Penn study6 analyzed association with cannabis criterion counts, and the cannabis-dependence meta-analysis7 used cannabis-exposed individuals as controls in their study. In addition, the composition of the cohorts analyzed also differs: the previous GWASs6,7 were based on cohorts established to study genetics of substance use disorders while the
