We constructed polygenic scores (PGS), which are aggregate measures of the number of risk alleles individuals carry weighted by effect sizes from GWAS summary statistics, from six recent GWAS of SUDs and comorbid conditions including: (1) externalizing problems (EXT) [31]; (2) depression (DEP) [32]; (3) problematic alcohol use [33] (ALCP); (4) alcohol consumption (drinks per week, ALCC) [34, 35]; (5) cigarettes per day/FTND (CPD); [34, 36] and (6) schizophrenia (SCZ) [37, 38]. We focused on these PGS, specifically, because: (1) SUDs show strong genetic overlap with other externalizing [39–41], internalizing [32, 42], and psychotic disorders [33, 43, 44]; (2) both shared and substance-specific genetic risk are associated with later SUDs [45–47]; and (3) substance use and SUDs have only partial genetic overlap [48, 49]. Therefore, our PGS cover a spectrum of genetic risk for SUDs, using the most current and well-powered results for each of the listed domains (see supplementary information section 4 for a detailed description).
