Cannabis use and misuse are heritable (h2=50–70% of the variation). Several genomewide association studies (GWAS) have attempted to identify loci that might contribute to this heritable variation12–18. For cannabis use, the largest published study to date (N = 184,765 individuals of European descent19; results used here on n=162,082; see Supplemental Materials for details) identified four independent genomewide significant loci and found a genomewide single nucleotide polymorphism (SNP) heritability of 10%, suggesting that the aggregated effects of common SNPs captured a sizeable portion of the heritability of cannabis use. Polygenic risk scores (PRS) offer a complementary approach to the study of such aggregated effects20. In brief, a PRS is a person-specific index of genetic propensity to a trait (e.g., cannabis use); PRS are constructed by multiplying the effect size from a discovery GWAS by the number of risk alleles that an individual possesses at that SNP. PRS approaches are widely used in psychiatric genetics, including substance use and dependence, and can be used to assess whether genetic risk for one disorder or trait is associated with aspects of the same trait,
