We used cross-trait LD-Score regression62 to estimate the genetic correlation between lifetime cannabis use and 25 other traits using GWAS summary statistics. The genetic covariance is estimated using the slope from the regression of the product of z-scores from 2 GWASs on the LD score. The estimate represents the genetic covariation between the 2 traits based on all polygenic effects captured by SNPs. Summary statistics from well-powered GWASs were available for 25 relevant substance use and mental health traits, including nicotine, alcohol and caffeine use, schizophrenia, depression, bipolar disorder, and loneliness (Supplementary Table S6). To correct for multiple testing we adopted a Bonferroni corrected p-value threshold of significance of 0.002 (0.05/25). LD scores were based on the HapMap 3 reference panel, restricted to European populations.
