Polygenic risk profile scores were constructed using the p-values and log10 odds ratios from the most recent large genome-wide association study of schizophrenia, a meta-analysis of the Psychiatric Genomics Consortium’s studies with additional Swedish samples totaling 13,833 cases and 18,310 controls27. SNPs were pruned for linkage disequilibrium using p-value informed clumping in PLINK37, using a cut-off of R2 =0.25 within 200kb window. The MHC region of the genome was excluded, due to its complex linkage disequilibrium structure. After linkage disequilibrium pruning 147,830 SNPs remained. Multiple scores were generated for each individual using the PLINK --score option and based on top SNPs from the schizophrenia GWAS using varying significance thresholds (p=0.0001, 0.001, 0.01. 0.05, 0.1, 0.2, 0.3, 0.4, 0.5, and 1.0). Polygenic risk profile scores were tested for association with a binary ever vs. never used cannabis and two quantitative traits for quantity of use and age at first use, in logistic and linear regressions respectively. These analyses were corrected for the first 10 ancestry-informative principal components, genotyping platform, sex, age, age squared, and sex-by-age. Analysis was performed in STATA38.
