Summary: A new genetically informed study from the University of Oslo, published in Lancet Psychiatry, finds that cannabis use and certain psychiatric disorders—including schizophrenia and bipolar disorder—share common genetic influences. Using advanced statistical models, the researchers show a complex pattern in which many genetic variants raise the risk of both cannabis use and psychotic disorders, while a smaller set of variants exerts opposing effects. These results clarify part of the link between cannabis and mental health and carry implications for prevention, personalized care, and future treatment development.
The analysis suggests that a genetically defined subgroup of people may be predisposed to both cannabis use and psychotic disorders. By identifying shared genetic loci and biological pathways, the study provides evidence that the association between cannabis and psychosis may be driven partly by inherited susceptibility, not solely by exposure to the drug.
Key facts:
- The study finds overlapping genetic factors that influence susceptibility to cannabis use and psychiatric disorders such as schizophrenia and bipolar disorder.
- Most shared genetic variants appear to increase risk for both cannabis use and psychotic disorders, but some variants show opposing effects—raising the risk for cannabis use while lowering the risk for schizophrenia or bipolar disorder.
- Understanding this genetic overlap can inform prevention strategies, risk stratification, and the development of more targeted treatments for mental health conditions.
Source: University of Oslo
Researchers led by Drs. Weiqiu Cheng and Nadine Parker analyzed large-scale genome-wide association data to explore the genetic relationships between lifetime cannabis use, cannabis use disorder, schizophrenia, and bipolar disorder. Their work combined data from multiple international cohorts, including the Psychiatric Genomics Consortium, UK Biobank, and the International Cannabis Consortium, focusing on participants of European ancestry to estimate heritability, polygenicity, and discoverability for each phenotype.
The investigators report positive genome-wide genetic correlations between psychotic disorders and cannabis-related phenotypes, with correlation estimates ranging from 0.22 to 0.35. At the same time, local genetic correlations varied across the genome, showing both positive and negative associations. Depending on the pair of traits compared, the analysis identified between three and 27 shared loci that map to genes enriched for neuronal and olfactory cell types and for known drug–gene interactions involving nicotine, alcohol, and duloxetine.
Using causal inference methods and polygenic risk scoring in the Norwegian Thematically Organized Psychosis cohort, the study found evidence that genetic liability to psychotic disorders has a causal effect on cannabis phenotypes, and that lifetime cannabis use has a causal effect on bipolar disorder. In polygenic score analyses involving 2,181 European participants (mean age 33.1 years), scores derived from cannabis-related genetics improved prediction of psychotic disorders beyond scores built from psychotic disorder genetics alone.
Lead author Weiqiu Cheng summarizes the implications: “There is a shared genetic basis underlying our susceptibility to both cannabis use and certain psychiatric disorders. These findings point to a subgroup of individuals who are genetically at higher risk for both.” Coauthor Nadine Parker adds that the complex pattern of shared and opposing genetic effects suggests biological mechanisms that might partly explain both harmful and potentially beneficial effects of cannabis-related compounds.
The authors note several clinical and public-health implications. First, genetic information could help target preventative measures and reduce cannabis exposure among individuals at elevated genetic risk for schizophrenia or bipolar disorder. Second, investigating the biological pathways implicated by shared loci may reveal targets for new, more precise treatments. Third, improved genetic stratification could support personalized treatment plans for people with psychotic disorders who also use cannabis.
About this genetics and mental health research news
Author: Press Office
Source: University of Oslo
Contact: Press Office – University of Oslo
Image: The image is credited to Neuroscience News
Original Research: Closed access.
“The relationship between cannabis use, schizophrenia, and bipolar disorder: a genetically informed study” by Weiqiu Cheng et al., Lancet Psychiatry.
Abstract
The relationship between cannabis use, schizophrenia, and bipolar disorder: a genetically informed study
Background
The link between psychotic disorders and cannabis use is a subject of ongoing debate. Shared genetic risk is one plausible explanation for observed associations. This study investigates genetic overlap between psychotic disorders (schizophrenia and bipolar disorder) and cannabis phenotypes (lifetime cannabis use and cannabis use disorder).
Methods
Genome-wide association summary statistics from European-ancestry participants were analyzed to estimate heritability, polygenicity, and discoverability for each trait. The team performed genome-wide and local genetic correlation analyses, identified shared loci and mapped them to genes for functional enrichment analysis, and used causal inference approaches and polygenic scores applied to the Norwegian Thematically Organized Psychosis cohort.
Findings
Psychotic disorders were found to be more heritable and more polygenic than cannabis phenotypes. Positive genome-wide genetic correlations between psychotic disorders and cannabis traits ranged from 0.22 to 0.35, while local correlations included both positive and negative signals. The researchers identified between three and 27 shared loci across trait pairs, with mapped genes showing enrichment in neuronal and olfactory cell types and known drug–gene targets.
Causal analyses indicated that genetic liability to psychotic disorders influences cannabis-related phenotypes and that lifetime cannabis use may exert a causal effect on bipolar disorder. In the Norwegian cohort, polygenic scores for cannabis phenotypes predicted psychotic disorders and added predictive value beyond psychotic-disorder-specific scores.
Interpretation
A subgroup of individuals may carry a high genetic risk for both psychotic disorders and cannabis use. These results support public-health efforts to reduce cannabis exposure—particularly among at-risk individuals and patients with psychotic disorders—and highlight shared genetic loci that could guide future treatment research.
Funding
Funding sources included the US National Institutes of Health, Research Council Norway, South-East Regional Health Authority, Stiftelsen Kristian Gerhard Jebsen, EEA-RO-NO-2018–0535, the European Union’s Horizon 2020 programme, Marie Skłodowska-Curie Actions, and University of Oslo Life Science.