Polygenic risk scores reveal genetic underpinnings of comorbidity between substance use disorders and ADHD

One in five people attending services with a substance use disorder (SUD) also has comorbid attention-deficit/hyperactivity disorder (ADHD). While some evidence shows that shared heritability might partly explain this frequent comorbidity, studies on this topic are scarce. Therefore, the goal of this study was to test whether ADHD and SUD have shared genetic influences. A total of 1,513 SUD treatment-seeking individuals of European ancestry were included in the study. Polygenic risk scores (PRS) were applied to test a) the association of the PRS for ADHD with multiple SUD-related phenotypes, and b) the association of the PRS for SUDs (alcohol, cocaine, cannabis, opioid, and polysubstance use disorder) with ADHD-related phenotypes. Causality between ADHD traits and SUD-related phenotypes was tested by using one-sample Mendelian randomization analyses. PRS for ADHD significantly increased the likelihood of ever using heroin (R2 = 0.7 %, p < 0.001, ß = 0.20, SE = 0.06). PRS for opioid use disorder was significantly associated with ADHD inattentive symptoms (R2 = 0.6 %, p = 0.018, ß = 0.08, SE = 0.02) and with ADHD total symptom score (R2 = 0.6 %, p = 0.025, ß = 0.07, SE = 0.02). No evidence of causal relationships were found. The findings of this study highlight the genetic contribution to the relationship between ADHD and SUDs with some indication of overlap, particularly between ADHD and opioid use disorder.