In the EUR data, we found that a common genetic factor model with DSM-NicDep, PAU, OUD, and CanUD as indicators, similar to the Addiction-Risk-Factor presented in Hatoum et al.4, fit the data well (Figure 2A; Supplemental Table 6). There were two differences between the Hatoum et al. Addiction-Risk-Factor and our modified model: (1) we used larger, more recent versions of the OUD26, PAU24, and CanUD25 GWASs; and (2) we removed the residual correlation between PAU and OUD, as this path was no longer significant. We compared the model with DSM-NicDep as the tobacco-related indicator (Figure 2A) to one where DSM-NicDep was substituted by the original problematic tobacco use (PTU) GWAS meta-analysis (FTND + CPD) from Hatoum et al.4 (Figure 2B; Supplemental Table 7), and one where NicDep was substituted by ICD-TUD6 (Figure 2C; Supplemental Table 8). Each of the modified models fit the data well, but the loading for DSM-NicDep was the largest of the three tobacco-related indicators, almost 3-fold larger than the loading for PTU in the equivalent model (0.86 vs. 0.30).
