Phenotypic and genetic relations between attention-deficit/hyperactivity disorder and substance use disorders.

Authors

Michael Setzer, Rachel Kember, Emily Hartwell, Zachary Piserchia, Joel Gelernter, Henry Kranzler, Joshua Gray

Published in

Psychological medicine. Volume 56. Pages e281. Sep 18, 2026. Epub Sep 18, 2026.

Abstract

Attention-deficit/hyperactivity disorder (ADHD) and substance use disorders (SUDs) commonly co-occur and have overlapping genetic liabilities. Less is known regarding the phenomenology and genetics of ADHD in a cohort enriched for SUDs and the extent to which ADHD genetic liability contributes to SUD risk when controlling for substance specific genetic risk.
We used data from the Yale-Penn cohort, which comprises ~14,000 individuals ascertained for SUDs and/or as controls. Psychiatric and substance use phenotypes were ascertained from the semi-structured assessment for drug dependence and alcohol survey for all participants. Polygenic scores (PGSs) were developed for ADHD and multiple substance-related traits using summary statistics from large genome-wide association studies on participants with genetic data (N = 10,275).
Participants who met DSM-IV Criteria for ADHD had significantly increased odds for every DSM-5 SUD analyzed, greater polysubstance use, and younger age of onset of substance use. Among participants of European-like ancestry, ADHD PGS was associated with multiple SUDs, even after controlling for substance-specific PGS. Of the substance-related PGS, only the smoking initiation PGS was associated with ADHD diagnosis and criterion count and only among individuals of European-like ancestry.
In this sample, ADHD was associated with increased risk for SUDs and earlier onset of substance use. Additionally, genetic liability to ADHD was independently associated with multiple SUDs and SUD criteria counts. PGS for substance-related traits tended to be less significantly associated with ADHD. Further studies in large, diverse populations are needed to enhance our understanding of these associations.

PMID:
42755248
Bibliographic data and abstract were imported from PubMed on 18 Sep 2026.

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