In summary, our analyses highlight the importance of considering diagnostic assessment in genetic studies of substance use disorders. We found that DSM-NicDep was more closely related to a general addiction liability factor compared to a “PTU” phenotype that combined FTND and CPD. The DSM-NicDep PGS was significantly associated with ICD-TUD in an independent biobank and was associated with individual DSM-5 TUD criteria in another independent sample. Compared to FTND, DSM-NicDep was more strongly genetically correlated with ICD-TUD, PAU, SmkInit, cannabis ever-use, and material deprivation. Given the strong genetic correlation between DSM-NicDep and ICD-TUD, future analyses may consider combining data from DSM-NicDep and ICD-based studies of TUD to maximize sample size for gene discovery.
