These results provide strong systematic evidence of shared polygenic risk between schizophrenia and substance use disorder. Each independent substance use disorder dataset showed a strong shared genetic architecture with a genetic liability to schizophrenia, and the signal was greatly strengthened when all substance use disorders were considered together. However, because of comorbidity among the substance use disorder diagnoses, we cannot statistically test whether the observed association is driven by tobacco use disorder or a general substance use disorder liability. It is well known that substance use disorders are often comorbid with one another, and family and twin studies have demonstrated that the underlying genetic liability to substance use disorder has both common and specific genetic risk factors (46–49).
