Twin studies indicate that 50-60% of the variation in cannabis use disorders (abuse/dependence, variously defined using DSM-IIIR, DSM-IV and ICD) can be attributed to heritable influences (Verweij et al., 2010). Despite this robust heritability estimate, association studies for cannabis use disorders have largely failed to identify genetic variants of significant and replicable effect. A prior genome-wide association study (GWAS) of DSM-IV cannabis dependence, conducted in the sample used in this study, failed to identify genetic variants at a statistically significant level (Agrawal et al., 2011b). This has resulted in speculation regarding the biological underpinnings of cannabis use disorders; in particular, the question of whether common variation available in commercially available genome-wide arrays captures it (Sullivan et al., 2012).
