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., (2022), fit the data well (Figure 2a and Supplemental Table 7). 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 OUD (Deak et al., 2022), PAU (Zhou et al., 2023), and CanUD (Levey et al., 2023) 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 PTU GWAS meta-analysis (FTND + CPD) from Hatoum et al.4 (Figure 2b and Supplemental Table 8), and one where NicDep was substituted by ICD-TUD (Toikumo et al., 2024) (Figure 2c and Supplemental Table 9). 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 threefold larger than the loading for PTU in the equivalent model (0.86 vs. 0.30).
