The lack of genome-wide significant associations for individual SNPs is consistent with previous GWA studies of lifetime cannabis use26, 27 and cannabis dependence.25 The difficulty of identifying specific SNPs for lifetime cannabis use may be attributable to several reasons. First, complex traits are known to be influenced by many variants, each with very small effect sizes. Although power calculations reveals suitable power (96%) to detect odds ratios of 1.15 based on common SNPs (MAF=0.2), the power to detect smaller effect sizes remains lower. For example, there is only 28% power to detect effect sizes with odds ratio of 1.1 and MAF=0.2. Therefore, our data suggest that the effect sizes of single variants contributing to lifetime cannabis use are likely to be smaller than 1.15. Combining variants within larger units (that is, genes) did however reveal four significant genes associated with lifetime cannabis use implying that these genes are appropriate targets for future functional studies of cannabis use. Unfortunately, our gene-based results were not replicated in the replication samples, probably due to low sample sizes and therefore low power. In the African American replication sample, we did find suggestive association with SCOC-AS1 and SCOC.
