Family and twin studies have shown that CaD has an important genetic component. The heritability of cannabis abuse or dependence was estimated to be 45–78% (9). Genomewide linkage studies (GWLS) and candidate gene association studies have identified a list of possible chromosomal risk regions and candidate genes for cannabis use disorders (9–16). For example, linkage studies have identified genomic regions harboring candidate genes with biological relevance, such as the monoacylglycerol lipase gene (MGLL) on chromosome 3 and the gamma-aminobutyric acid receptor subunit alpha-2 gene (GABRA2) on chromosome 4 (14). The cannabinoid receptor gene (CNR1) and several other genes (CRN2, FAAH, and MGLL), which are specific to the endogenous cannabinoid system, have been selected for candidate gene association studies, although the results were largely inconclusive (14). Recently, a genomewide association study (GWAS) for CaD was conducted in 708 individuals with DSM-IV CaD cases and 2346 cannabis-exposed non-dependent controls, using a GWAS dataset from the Study of Addiction: Genetics and Environment (SAGE) (17). However, no results achieved genomewide significance in this study. Despite the effort that has been made in gene mapping for CaD, genetic factors underlying CaD susceptibility remain largely unknown.
