On the basis of twin studies, the heritability of lifetime cannabis use is estimated at 40–50%.12 In our study, all common SNPs combined explained 13–20% of the variance in the liability to use cannabis depending on the method used. Stricter LD pruning (that is, r2=0.05) or restricting to SNPs observed (genotyped or imputed) in all the analyses, substantially reduces the estimate of variance explained. Speculatively, this may indicate that much of the variance explained comes from SNPs located in the regions of weak LD. Such effects are likely to be poorly tagged for the estimation of variance explained after strict LD pruning, and are likely to be more difficult to impute owing to a lack of strongly correlated genotyped SNPs (and thus missing from some studies). Our SNP-based heritability estimates lie in between two previous heritability estimates for lifetime cannabis use based on the Genome-wide Complex Trait Analysis65 software package. Verweij et al.26 estimated that 6% of the variance in lifetime cannabis use is explained by aggregated common SNPs (MAF>0.05). Minică et al.27 found an estimate of 25%. Provided that
