SNP- and gene-based tests revealed several SNPs and genes strongly associated with lifetime cannabis use. Overall, 11% of the variation in the phenotype was explained by the combined effect of SNPs, which amounts to approximately 25% of twin-based heritability estimates 4. CADM2 and NCAM1, both identified in the original ICC meta-analysis 10, were among the strongest findings in the SNP-based and gene-based tests. The CADM2 gene (Cell Adhesion Molecule 2) is a synaptic cell adhesion molecule and is part of the immunoglobulin superfamily. Interestingly, CADM2 has previously been identified in GWASs of other behavioural phenotypes, including alcohol consumption 14, processing speed 29, and number of offspring and risk-taking behavior 16. A large-scale phenome-wide scan showed that CADM2 was associated with various personality traits, with the risk variant being associated with reduced anxiety, neuroticism and conscientiousness, and increased risk-taking 15. Taken together, these findings suggest that risk variants in CADM2 are associated with a broad profile of a risk-taking, optimistic, and care-free personality 15. Cannabis use has previously been associated with related personality traits, including high levels of impulsivity and novelty seeking 30,31.
