Review finds shared genetic links across cannabis and other substance disorders

Complex and common, substance use disorders (SUDs) are heterogeneous in presentation and difficult to treat. Moreover, SUDs are frequently comorbid with other psychiatric disorders and medical issues. While it is known that SUDs are moderately heritable, the underlying genetic etiology of SUDs and their comorbidities have remained elusive. Here, we synthesize findings from 2 types of datasets, namely electronic health record-based datasets and deeply phenotyped datasets, to examine genetic liabilities for substance use and associations with other phenotypes. Each dataset type brings unique strengths and limitations to our understanding of the genetics of SUDs. We review phenome-wide association studies of genetic liability for 4 common substances of abuse (alcohol, opioid, tobacco, and cannabis) as well as a transdiagnostic addiction factor. These analyses consistently identified associations with other substances, psychiatric disorders, demographic characteristics, and comorbid medical conditions. We conclude the review by proposing the ideal dataset and future directions for the field. Substance use disorders (SUDs) are common, complex, and co-occur with mental and physical health problems. We reviewed phenome-wide association studies that examined whether genes linked to alcohol, tobacco, opioid, and cannabis use disorders are also associated with other health conditions. Using electronic health records and deeply phenotyped datasets, these studies consistently found that genetic risk for each substance disorder is linked to psychiatric conditions such as depression, anxiety, and PTSD; to other SUDs; and to a range of medical conditions. We discuss what these findings tell us about shared biology and what kinds of data would best to advance the field.