We conducted a meta-analysis of GWAS data on individuals of European descent from five cohorts to identify loci associated with DSM-IV cannabis dependence (N=2,080). We compared individuals who met criteria for DSM-IV cannabis dependence (N=2,080) to controls who did not meet criteria for cannabis dependence but reported having used cannabis, at least once, during their lives (N=6,435). In addition to comprehensive locus (including epigenetic) annotation, we examined whether genomewide significant SNPs were associated with variability in gray matter volume within brain regions (bilateral amygdala, ventral striatum and hippocampus) previously associated with chronic cannabis use and misuse (14;15) among an independent cohort of 430 EA college students. Some prior studies have reported lower gray matter volume in these brain regions, although results are inconclusive. While a majority of studies have attributed such volumetric changes to the effects of chronic cannabis exposure (e.g.,(16)), at least one study has implicated common predisposing influences, such as genetic liability, as the major contributor to the association between casual cannabis use and variability in amygdala volume (17). As this sample of college students included <10 individuals
