Genetic Factors in Cannabinoid Use and Dependence.

Cannabinoid use and dependence are heritable traits controlled in part by genetic factors. Despite a high incidence of use worldwide, genes that contribute to the risk of problematic use and dependence remain enigmatic. Here we review human candidate gene association studies, family-based linkage studies, and genome-wide association studies completed within the last two decades. These studies have expanded the list of candidate genes and intervals. However, there is little overlap between studies and generally low reproducibility in independent samples. Reasons for this lack of coherence vary but may depend on low sample size and statistical power, and the fact that most studies leverage populations ascertained for drug dependence other than cannabis. However, recent well-powered studies on lifetime cannabis use demonstrate that the genetic architecture of cannabis use resembles that of other substance use disorders and psychiatric disease in that many small effect genes contribute in an additive fashion. This finding suggests that increasing sample size and more focused recruitment of individuals based on cannabinoid use and dependence will identify more candidate genes. Follow-up of existing high priority candidates in preclinical model systems will facilitate better understanding of the genetic architecture and genetic risk factors for cannabis use and dependence.