Reducing the widespread prevalence1–3 and devastating worldwide impact4,5 of alcohol and illicit drug dependence is hindered by limited etiologic insight that impedes prevention and treatment advances. In the United States (US), 12.5% of the population meets criteria for a lifetime history of alcohol dependence3 while 2.6% meet criteria for DSM-IV drug dependence during their lifetime2. Notably, individuals are often comorbid for multiple substance use disorders2, and common latent genetic factors6,7 explain a large proportion of the moderate to high heritability of dependence on individual substances (h2=50–70%8–10). The common genetic architecture of dependence liability is also underscored by evidence from genome-wide association studies (GWAS) documenting genetic correlations between alcohol-related measures and cannabis and cigarette use11,12. Leveraging the common genetic architecture underlying general substance dependence liability to identify markers of dependence risk through GWAS would complement existing efforts targeting individual substances (e.g., 12–16) to elucidate underlying etiologic risk factors for general and specific substance dependence liability.
