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Mol Psychiatry. 2019 Jan 4. doi: 10.1038/s41380-018-0339-3. [Epub ahead of print]

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

Author information

1
Psychiatric Genetics Unit, Group of Psychiatry, Mental Health and Addiction, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain. maria.soler@vhir.org.
2
Department of Psychiatry, Hospital Universitari Vall d'Hebron, Barcelona, Spain. maria.soler@vhir.org.
3
Biomedical Network Research Centre on Mental Health (CIBERSAM), Instituto de Salud Carlos III, Barcelona, Spain. maria.soler@vhir.org.
4
Psychiatric Genetics Unit, Group of Psychiatry, Mental Health and Addiction, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.
5
Department of Psychiatry, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
6
Biomedical Network Research Centre on Mental Health (CIBERSAM), Instituto de Salud Carlos III, Barcelona, Spain.
7
Department of Psychiatry and Legal Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain.
8
Department of Biomedicine-Human Genetics, Aarhus University, Aarhus, Denmark.
9
The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark.
10
Centre for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark.
11
Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU University Amsterdam, Amsterdam, The Netherlands.
12
Behavioural Science Institute, Radboud University, Nijmegen, The Netherlands.
13
Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
14
Stanley Center for Psychiatric Research and the Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
15
Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
16
Department of Psychiatry, Radboud University Medical Center, Nijmegen, The Netherlands.
17
Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands.
18
Departments of Psychiatry and of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, NY, USA.
19
Psychiatric Genetics Unit, Group of Psychiatry, Mental Health and Addiction, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain. marta.ribases@vhir.org.
20
Department of Psychiatry, Hospital Universitari Vall d'Hebron, Barcelona, Spain. marta.ribases@vhir.org.
21
Biomedical Network Research Centre on Mental Health (CIBERSAM), Instituto de Salud Carlos III, Barcelona, Spain. marta.ribases@vhir.org.

Abstract

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.

PMID:
30610198
DOI:
10.1038/s41380-018-0339-3

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