As this study is a direct extension of and requires comparison to results from our previous work 17,18, we retain the GWAS used in those studies as indicators in the current models. These indicators include: ADHD19, cannabis initiation (CANN)20, smoking initiation (SMOK)21, age at first sexual intercourse (FSEX)22, number of sexual partners (NSEX)22, risk taking propensity (RISK)22, problematic alcohol use (PAU)23, problematic tobacco use (PTU)9, opioid use disorder (OUD)24, and cannabis use disorder (CUD)25. Due to concerns about the use of FSEX as an externalizing indicator26,27 we rab sensitivity analyses leaving out this indicator, which indicated that it did not exert undue influence on the composition of the factor (see Supplementary Text and Supplementary Table 2 for more detail). All GWAS included only individuals whose genomes were most similar to those from reference panels sampled from Europe (hereafter referred to as “EUR”) with a total sample size of 2,219,357 unique individuals (Supplementary Table 3). After merging across the ten sets of summary statistics, 5,963,905 SNPs were available for analysis.
