PRS were generated from the PGC-PTSD Freeze 2 data [9] for European ancestry (EA) COGA participants (N = 3533) using PRS-cs [50]. We tested the association of the PGC-PTSD PRS with lifetime DSM-IV PTSD and substance (alcohol, cannabis, cocaine, opioid) dependence diagnoses, including sex (female = 1; male = 0), age, ancestral principal components, and genotype array as covariates in EA COGA participants. Next, exploratory analyses were performed to investigate interaction effects of lifetime alcohol dependence with PRS (i.e., PRS*sex, PRS*alcohol dependence diagnosis) given that alcohol dependence has been shown to increase the likelihood of being diagnosed with PTSD and other (non-alcohol) substance dependence [5]. Lifetime PTSD diagnosis and non-alcohol substance (cannabis, cocaine, opioid) dependence diagnoses were included simultaneously as outcomes in the pathway model to account for the correlation between these outcomes. All association analyses were conducted in MPlus [51], clustering for familial relatedness, and included cross-term interactions as covariates (e.g., PRS*sex, PRS*age, etc.), as these have been shown to potentially bias effects in analyses involving PRS [52]. In addition, including cross-term interactions allowed for the primary analysis to
