To date, this is the largest GWA study of lifetime cannabis use. We performed meta-analysis of the GWA results based on a discovery sample comprising 32 330 individuals from 13 cohorts, and a replication sample comprising 5627 subjects from four cohorts (including one African American cohort). There were no genome-wide significant SNP associations. However, heritability analyses revealed that between 13 and 20% of the variation in lifetime cannabis use could be explained by common SNPs. Moreover, gene-based tests of association identified four protein-coding genes and one intergenic region significantly associated with lifetime cannabis use including NCAM1, which has previously been linked to substance use.45, 46, 47, 48 Finally, we revealed that the genetic liability to lifetime cannabis use correlated to a large extent (r=0.83) with the genetic liability to lifetime cigarette smoking. Our results are consistent with the hypothesis that lifetime cannabis use is a highly polygenic trait, comprising many SNPs each with small effects contributing to lifetime risk. Moreover, portions of the genetic risk in lifetime cannabis use likely correlates with other substances including cigarette smoking.
