Our study detected association signal in the measured SNPs. A comparison with prior SNP-heritability estimates suggests that at least part of the signal is likely coming from previously untyped common and from low frequency variants. The lack of genomewide significant results for the single variant and gene-based association tests suggests that initiation is a polygenic trait characterized by variants of very small effect (i.e., <1 % explained phenotypic variance). The causal variants are likely distributed over much of the genome, in proportion to the chromosomes’ length. Our results do not rule out the contribution of rare variants of larger effect imperfectly tracked by the measured SNPs—a plausible source of the difference between the twin-based heritability estimate and that from GCTA. Powerful analytic strategies and very large samples combined with considering the contribution of rare variants (MAF < 1 %) will allow one to further understand the causes of individual differences in the liability to initiate cannabis use.
