Linkage analysis rarely isolates a single gene. Rather, it narrows the investigator's search to a smaller region of the genome [19]. The search to identify specific genes (often more than one) within a linkage region (sometimes referred to as a ‘LOD-support’ region) requires information on the functional significance of genes in this chromosomal region and in some instances, fine-mapping of the region. There have been three published linkage studies of cannabis use disorders [20-22], and one of earlier stages of cannabis use (including frequency of use) [23] the key findings of which are presented in Table 1. The first of these, by Hopfer and colleagues [20], identified linkage regions for cannabis dependence symptoms in adolescents on chromosome 3 and 9. Under their linkage peak on chromosome 3 is the monoglyceride lipase gene (MGLL) which encodes an enzyme that has been found to hydrolyze the endocannabinoids 2-arachidonoylethanolamide and 2-arachidonoylglycerol (two naturally occurring substances that act on cannabinoid receptors on the brain). In other studies, genes were identified on chromosome 1 [22] and 14 [21]. The genes near these linkage peaks, however,
