Attention-deficit/hyperactivity disorder and lifetime cannabis use: genetic overlap and causality

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  • María Soler Artigas, Autonomous University of Barcelona, Vall d'Hebron University Hospital, CIBER - Center for Biomedical Research Network
  • ,
  • Cristina Sánchez-Mora, Autonomous University of Barcelona, Vall d'Hebron University Hospital, CIBER - Center for Biomedical Research Network
  • ,
  • Paula Rovira, Autonomous University of Barcelona, Vall d'Hebron University Hospital
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  • Vanesa Richarte, Vall d'Hebron University Hospital, CIBER - Center for Biomedical Research Network, Autonomous University of Barcelona
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  • Iris Garcia-Martínez, Autonomous University of Barcelona, Vall d'Hebron University Hospital
  • ,
  • Mireia Pagerols, Autonomous University of Barcelona, Vall d'Hebron University Hospital
  • ,
  • Ditte Demontis
  • Sven Stringer, Vrije Universiteit Amsterdam
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  • Jacqueline M. Vink, Radboud University of Nijmegen
  • ,
  • Anders D. Børglum
  • Benjamin M. Neale, Massachusetts General Hospital, Boston, Broad Institute
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  • Barbara Franke, Radboud University Nijmegen Medical Centre, Radboud University of Nijmegen
  • ,
  • Stephen V. Faraone, State University of New York Upstate Medical University
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  • Miguel Casas, Autonomous University of Barcelona, Vall d'Hebron University Hospital, CIBER - Center for Biomedical Research Network
  • ,
  • Josep Antoni Ramos-Quiroga, Autonomous University of Barcelona, Vall d'Hebron University Hospital, CIBER - Center for Biomedical Research Network
  • ,
  • Marta Ribasés, Autonomous University of Barcelona, Vall d'Hebron University Hospital, CIBER - Center for Biomedical Research Network
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  • ADHD Group of the Psychiatric Genomics Consortium, International Cannabis Consortium
  • ,
  • International Cannabis Consortium

Attention-deficit/hyperactivity disorder (ADHD) is a severely impairing neurodevelopmental disorder with a prevalence of 5% in children and adolescents and of 2.5% in adults. Comorbid conditions in ADHD play a key role in symptom progression, disorder course and outcome. ADHD is associated with a significantly increased risk for substance use, abuse and dependence. ADHD and cannabis use are partly determined by genetic factors; the heritability of ADHD is estimated at 70–80% and of cannabis use initiation at 40–48%. In this study, we used summary statistics from the largest available meta-analyses of genome-wide association studies (GWAS) of ADHD (n = 53,293) and lifetime cannabis use (n = 32,330) to gain insights into the genetic overlap and causal relationship of these two traits. We estimated their genetic correlation to be r2 = 0.29 (P = 1.63 × 10−5) and identified four new genome-wide significant loci in a cross-trait analysis: two in a single variant association analysis (rs145108385, P = 3.30 × 10−8 and rs4259397, P = 4.52 × 10−8) and two in a gene-based association analysis (WDPCP, P = 9.67 × 10−7 and ZNF251, P = 1.62 × 10−6). Using a two-sample Mendelian randomization approach we found support that ADHD is causal for lifetime cannabis use, with an odds ratio of 7.9 for cannabis use in individuals with ADHD in comparison to individuals without ADHD (95% CI (3.72, 15.51), P = 5.88 × 10−5). These results substantiate the temporal relationship between ADHD and future cannabis use and reinforce the need to consider substance misuse in the context of ADHD in clinical interventions.

Original languageEnglish
JournalMolecular Psychiatry
Volume25
Issue10
Pages (from-to)2493-2503
Number of pages11
ISSN1359-4184
DOIs
Publication statusPublished - 2020

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