While many large GWAS meta-analyses of substance use disorders have relied on cases defined using clinical criteria recommended by DSM or ICD classification, the few GWAS of DSM-NicDep to date have been relatively small7. We conducted a large meta-analysis of DSM-NicDep, combining data across 16 cohorts and multiple genetic ancestries. The largest analyses of psychiatric traits have focused on individuals whose genetics most closely resemble the European ancestry subset of the 1000 genomes project, so we assessed the genetic correlations between DSM-NicDep and other substance use phenotypes, psychiatric disorders, and related phenotypes in that subset. We also compared the correlations of the various nicotine dependence related measures (DSM-NicDep, ICD-TUD, and PTU) and other substance use disorders (cannabis use disorder, problematic alcohol use, and opioid use disorder) by fitting a previously published common factor model (the Addiction-risk-factor15) to the data using genomic structural equation modeling. Finally, we tested whether a polygenic score for DSM-NicDep was associated with DSM-5 tobacco use disorder and its 11 diagnostic criteria, and 4 of the 6 FTND criteria, in a large, independent sample, the National Epidemiologic Survey on Alcohol and Related Conditions-III (NESARC-III) cohort.
