We used mtCOJO [24] to individually condition the POU summary statistics on loci associated with other comorbid traits, including risk-taking behavior [27], smoking [28], cannabis use disorder [29], alcohol dependence [30], chronic pain [31], and OUD [32]. This analysis allowed us to examine whether the genetic associations with POU would be preserved when controlling for those covariate phenotypes. To test as many SNPs while preserving computational efficiency, we used a p value threshold of 2.00E−05, 5.00E−08,1.00E−05, 1.00E−05, 5.00E−08, and 1.00E−05, respectively, for risk-taking behavior, smoking, cannabis use disorder, alcohol dependence, chronic pain, and OUD. We then computed genetic correlations using the POU summary statistics adjusted for the covariates of interest.
