ICD and DSM criteria focus on physical and psychological (and social, in DSM-5) impairment due to substance use, and are, for the most part, identical across substances. FTND, on the other hand, places greater emphasis on physiological aspects of dependence (e.g., items related to tolerance and withdrawal12). Because most GWAS of substance use disorders utilize ICD and DSM criteria, we hypothesized that this discrepancy might underlie the lower genetic correlation observed between nicotine dependence and other substance use disorders in prior twin and genome-wide correlation studies that used FTND6. Indeed, the loading for DSM-NicDep in the Addiction-Risk-Factor genomic SEM was nearly 3 times that of the loading for PTU (0.83 vs. 0.30) (Figure 1). Notably, the loadings for OUD and PAU also increased in our model (0.83 to 1.0, and 0.58 to 0.81, respectively), likely due to the larger sample sizes of these more recent GWAS. We also noted no significant residual correlation between OUD and PAU in our analysis.
