We calculated the addiction-rf PRS using the PRS-cs auto approach70. This method assumes a general distribution of effect sizes across the genome, and then reweights SNPs based on this assumption, their effect size in the original GWAS, and their linkage disequilibrium (LD); weights for every SNP were then summed to create a final score. PRS were associated with phenotypes (OUD, TD, CUD, AUD, CoUD) in Yale-Penn 3 via a logistic regression controlling for first 10 PCs, age, sex and age by sex. PRS were scaled to unit variance. These logistic regression analyses were also examined for the following contrasts: 1) Those with any SUD (n=985) vs those with no SUD (n=1,001), to represent Any SUD; 2) Those with ≥2 SUDs (n=729) vs those with <2 (including 0) SUDs (n=1,257) to represent Polysubstance Use Disorder (PSUD); and 3) Those with ≥2 SUDs (n=729) vs those with 1 SUD (n=256) to represent PSUD within those with SUD. The association between the addiction-rf PRS and the SUD Common Factor was estimated with lavaan52 where a common factor loaded on the 5 disorders.
