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.

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Publication Details

Journal
European Neuropsychopharmacology
Published
2026-02-27
DOI
https://doi.org/10.1016/j.euroneuro.2026.112799
Citations
1
Primary Topic
Attention Deficit Hyperactivity Disorder
Type
article
Field-Weighted Citation Impact
33.12
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article

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

Sharlene Kaye, Christoffer Brynte, Lisa I. Horstman, Frieda Matthys et al.
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European Neuropsychopharmacology
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article

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

Sharlene Kaye, Christoffer Brynte, Lisa I. Horstman, Frieda Matthys, Judit Cabana Domínguez, Máté Kapitány‐Fövény, Steve Allsop, Johan Franck, Ábel Fóthi, Geert Dom, Lara Grau-López, Natalia Llonga, Romain Icick, Csaba Barta, Dora Koller, Josep A. Ramos-Quiroga, Wim van den Brink, Florence Vorspan, Katelijne van Emmerik-van Oortmerssen, Arnt Schellekens, Zsolt Demetrovics, Michael Farrell
article en
1 citations

Abstract

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.

European NeuropsychopharmacologyVol. 107
Semmelweis University (HU), Eötvös Loránd University (HU), Australian National University (AU), Universitat Autònoma de Barcelona (ES), Vrije Universiteit Brussel (BE), Radboud University Nijmegen (NL), University of Antwerp (BE), Inserm (FR), Flinders University (AU), Université Paris Cité (FR), Radboud University Medical Center (NL), Karolinska Institutet (SE), UNSW Sydney (AU), Assistance Publique – Hôpitaux de Paris (FR), Vall d'Hebron Institut de Recerca (ES), Institute of Biochemistry (HU), Radboud Institute for Molecular Life Sciences (NL), Nijmegen Institute for Scientist Practitioners in Addiction (NL), Vall d'Hebron Hospital Universitari (ES), GGZ inGeest (NL), Mental Health Commission (AU), Amsterdam University Medical Centers (NL), Medical Research Network (US), Universitat de Barcelona (ES), University of Amsterdam (NL)
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Attention Deficit Hyperactivity Disorder
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