None of the tested genes achieved genomewide significance (P < ~4.3 × 10−7). However, our results have pinpointed several possible candidate genomic regions, likely to have a bearing on the early stage of cannabis use. To name a few, the ZNF181 and the ZNF766 genes, both located on chromosome 19, yielded the strongest association signal in the gene-based analysis of initiation (i.e., P = 3.7 × 10−6, 1.1 × 10−4, respectively). According to the GO annotations, ZNF181 and ZNF766 are functional genes belonging to the zinc finger family of genes, being involved in nucleic acid binding and metal ion binding. The most strongly associated genes with age at onset were the protein coding genes GEMIN5 (P = 4.7 × 10−4) on chromosome 5 and MT4 on chromosome 16 (P = 5.2 × 10−4). GEMIN5 plays a role in protein binding and snRNA binding, whereas MT4 is involved in copper ion and zinc ion binding. The role these genes play in initiation and age at onset has yet to be clarified, as none have been previously reported to be associated with cannabis use or other addiction phenotypes.
