The chromosome-by-chromosome analyses showed that, on average, longer chromosomes account for a larger amount of variance in initiation. This result lends support to the conclusion that initiation is highly polygenic. The largest amount of variance is explained by chromosome 4 (6.8 %; P = 0.002), followed by chromosome 18 (3.6 %; P = 0.012). Regions on both chromosome 4 and 18 have been reported to play a role in cannabis use and other addiction phenotypes. For instance, regions on chromosome 4 harboring the GABRA cluster of genes were identified in a linkage study by Agrawal et al. (Agrawal et al. 2008b) as plausibly associated with a cannabis abuse and dependence phenotype. Another linkage study (Prescott et al. 2006) provided strong evidence for a large region on chromosome 4 to be involved in alcohol dependence (P = 2.1 × 10−6), the same region being also reported by Uhl et al. to be associated with illicit drug abuse (Uhl et al. 2002). Regions on chromosome 18 were suggested to harbor GVs potentially associated with initiation of cannabis use (Agrawal et al. 2008a),
