We found 17 genomic loci significantly associated with addiction-rf, and 47 substance-specific loci. Post hoc fine-mapping, annotation, and exploratory drug repurposing analyses highlight the potential therapeutic relevance of the discovered loci. The addiction-rf PRS was associated with many medical conditions characterized by high morbidity and mortality rates, including psychiatric illnesses, self-harming behaviors, and somatic diseases that could be consequences of chronic substance use (e.g., chronic airway obstruction) or precursors to heavy substance use (e.g., chronic pain). Finally, in a sample of drug-naïve children, the addiction-rf PRS was correlated with parental substance use problems and externalizing behavior.
