Genetic correlations revealed substantial levels of pleiotropy with traits that often co-occur with TUD, including other substance use and psychiatric disorders. These associations were particularly evident in the Yale-Penn sample,47 which has comprehensive phenotypic data for substance use disorders. In adult patients from the Mayo Clinic, we replicated the associations with substance and other psychiatric disorders, extending them to medical disorders, such as HIV, heart disease, and pain, some of which (e.g., respiratory conditions) likely reflect chronic smoking. The positive associations between genetic liability for TUD and other outcomes, such as BMI and other internalizing/externalizing problems in tobacco-naive children (ABCD), may also reflect true biological relationships. Although we are far from untangling this complex web of genetic and non-genetic correlations, the extensive phenotypic spectrum associated with TUD is undeniable.
