We used linkage disequilibrium score regression (LDSC22,23) to estimate the SNP-heritability of DSM-NicDep and the genetic correlations between DSM-NicDep and other substance use phenotypes, using published GWASs of problematic alcohol use (PAU24), Fagerström Test for Nicotine Dependence (FTND4), ICD-based tobacco use disorder (ICD-TUD6), problematic tobacco use (PTU, a combination of FTND and cigarettes per day15), cannabis use disorder (CanUD25), opioid use disorder (OUD26), smoking initiation 3, smoking cessation 3, and cigarettes per day3. We also estimated genetic correlations between DSM-NicDep and other phenotypes including psychiatric disorders, behavioral traits, respiratory health, and socioeconomic status-related phenotypes. Details on the individual GWAS used in genetic correlation analyses are provided in the Supplemental Methods. We further tested whether genetic correlations for DSM-NicDep and FTND were different from each other using a block-jackknife method23,27.
