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No evidence of associations between genetic liability for schizophrenia and development of cannabis use disorder

Published online by Cambridge University Press:  09 December 2019

Carsten Hjorthøj Open the ORCID record for Carsten Hjorthøj [Opens in a new window] ,
Md Jamal Uddin ,
Theresa Wimberley ,
Søren Dalsgaard ,
David M. Hougaard ,
Anders Børglum ,
Thomas Werge  and
Merete Nordentoft
Carsten Hjorthøj*
Affiliation:
Copenhagen Research Center for Mental Health – CORE, Mental Health Center Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Copenhagen and Aarhus, Denmark Department of Public Health, Section of Epidemiology, University of Copenhagen, Copenhagen, Denmark
Md Jamal Uddin
Affiliation:
Copenhagen Research Center for Mental Health – CORE, Mental Health Center Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Copenhagen and Aarhus, Denmark
Theresa Wimberley
Affiliation:
The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Copenhagen and Aarhus, Denmark Department of Economics and Business Economics, NCRR-The National Centre for Register-Based Research, Aarhus BSS, Aarhus University, Aarhus, Denmark CIRRAU-Centre for Integrated Register-Based Research, Aarhus University, Aarhus, Denmark
Søren Dalsgaard
Affiliation:
The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Copenhagen and Aarhus, Denmark Department of Economics and Business Economics, NCRR-The National Centre for Register-Based Research, Aarhus BSS, Aarhus University, Aarhus, Denmark
David M. Hougaard
Affiliation:
The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Copenhagen and Aarhus, Denmark Department for Congenital Disorders, Center for Neonatal Screening, Statens Serum Institute, Copenhagen, Denmark
Anders Børglum
Affiliation:
The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Copenhagen and Aarhus, Denmark Institute of Human Genetics, University of Aarhus, Aarhus, Denmark
Thomas Werge
Affiliation:
The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Copenhagen and Aarhus, Denmark Research Institute of Biological Psychiatry, Mental Health Center Sanct Hans, Copenhagen University Hospital, Roskilde, Denmark
Merete Nordentoft
Affiliation:
Copenhagen Research Center for Mental Health – CORE, Mental Health Center Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Copenhagen and Aarhus, Denmark
*
Author for correspondence: Carsten Hjorthøj, E-mail: Carsten.hjorthoej@regionh.dk
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Abstract

Background

Cannabis use and cannabis use disorder (CUD) is increased in patients with schizophrenia. It is important to establish if this is explained by non-causal factors, such as shared genetic vulnerability. We aimed to investigate whether the polygenic risk scores (PRS) for schizophrenia and other psychiatric disorders would predict CUD in controls, patients with schizophrenia, and patients with other psychiatric disorders.

Methods

We linked nationwide Danish registers and genetic information obtained from dried neonatal bloodspots in an observational analysis. We included people with schizophrenia, other psychiatric disorders, and controls. The exposures of interest were the PRS for schizophrenia, attention-deficit hyperactivity disorder (ADHD) autism spectrum disorder, and anorexia nervosa. The main outcome of interest was the diagnosis of CUD.

Results

The study included 88 637 individuals. PRS for schizophrenia did not predict CUD in controls [hazard ratio (HR) = 1.16, 95% CI 0.95–1.43 per standard-deviation increase in PRS, or HR = 1.47, 95% CI 0.72–3.00 comparing highest v. remaining decile], but PRS for ADHD did (HR = 1.27, 95% CI 1.08–1.50 per standard-deviation increase, or HR = 2.02, 95% CI 1.27–3.22 for the highest decile of PRS). Among cases with schizophrenia, the PRS for schizophrenia was associated with CUD. While CUD was a strong predictor of schizophrenia (HR = 4.91, 95% CI 4.36–5.53), the inclusion of various PRS did not appreciably alter this association.

Conclusion

The PRS for schizophrenia was not associated with CUD in controls or patients with other psychiatric disorders than schizophrenia. This speaks against the hypothesis that shared genetic vulnerability would explain the association between cannabis and schizophrenia.

Keywords

Cannabisgeneticspleiotropypolygenic riskschizophrenia
Type
Original Articles
Information
Psychological Medicine , Volume 51 , Issue 3 , February 2021 , pp. 479 - 484
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Copyright
Copyright © Cambridge University Press 2019

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