Genetic Risk for Cannabis Use Disorder Independently Linked to Schizophrenia
Polygenic scores for cannabis use disorder predicted schizophrenia risk even in people without documented cannabis use, suggesting shared genetic factors rather than a purely causal relationship.
Quick Facts
What This Study Found
Both cannabis use disorder and schizophrenia polygenic scores independently predicted schizophrenia diagnosis. Notably, genetic liability for cannabis use disorder was associated with schizophrenia even in individuals with no documented history of cannabis use, pointing to widespread pleiotropy (shared genetic pathways).
Key Numbers
Cannabis use disorder polygenic scores significantly predicted schizophrenia across case definitions. The schizophrenia polygenic score effect on cannabis use was very modest. CUD genetic liability predicted schizophrenia even in people without documented cannabis use.
How They Did This
Researchers used genetic and health data from the All of Us Research Program to test whether polygenic scores for cannabis use disorder and schizophrenia independently predicted heavy cannabis use and schizophrenia diagnosis. They tested multiple case definitions to account for comorbidity.
Why This Research Matters
The cannabis-schizophrenia link has been debated for decades. This study used within-individual data on both genetics and diagnoses, addressing a key limitation of earlier work that lacked both measures in the same people.
The Bigger Picture
The relationship between cannabis and psychosis appears to involve shared genetics, not just one causing the other. Understanding these shared pathways could reshape how clinicians assess risk for both conditions.
What This Study Doesn't Tell Us
Preprint (not yet peer-reviewed). Cross-sectional design can't determine temporal ordering. Cannabis use history from medical records may be incomplete. Polygenic scores explain only a fraction of genetic risk.
Questions This Raises
- ?What specific genetic pathways are shared between cannabis use disorder and schizophrenia?
- ?Would these findings replicate in non-European ancestry populations?
Trust & Context
- Key Stat:
- CUD genetic risk predicted schizophrenia even without cannabis use history
- Evidence Grade:
- Moderate: large biobank with genetic and diagnostic data, but cross-sectional design and preprint status
- Study Age:
- 2025 preprint (medRxiv, not yet peer-reviewed)
- Original Title:
- Investigating the Polygenic Relationship Between Cannabis Use and Schizophrenia in the All of Us Research Program.
- Published In:
- medRxiv : the preprint server for health sciences (2025)
- Authors:
- Austin-Zimmerman, Isabelle(10), Thorpe, Hayley Ha, Meredith, John J(2), Khokhar, Jibran, Ge, Tian, Di Forti, Marta, Agrawal, Arpana, Johnson, Emma C, Sanchez-Roige, Sandra
- Database ID:
- RTHC-05977
Evidence Hierarchy
A snapshot of a population at one point in time.
What do these levels mean? →Frequently Asked Questions
Does this mean cannabis doesn't cause schizophrenia?
Not exactly. The study shows shared genetic factors contribute to both conditions, but it doesn't rule out that cannabis use could also increase risk. The relationship appears more complex than simple cause and effect.
What does pleiotropy mean in this context?
Pleiotropy means the same genes influence multiple traits. Here, some of the same genetic variants that increase risk for cannabis use disorder also increase risk for schizophrenia, independent of actual cannabis use.
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Cite This Study
https://rethinkthc.com/research/RTHC-05977APA
Austin-Zimmerman, Isabelle; Thorpe, Hayley Ha; Meredith, John J; Khokhar, Jibran; Ge, Tian; Di Forti, Marta; Agrawal, Arpana; Johnson, Emma C; Sanchez-Roige, Sandra. (2025). Investigating the Polygenic Relationship Between Cannabis Use and Schizophrenia in the All of Us Research Program.. medRxiv : the preprint server for health sciences. https://doi.org/10.1101/2025.05.20.25327979
MLA
Austin-Zimmerman, Isabelle, et al. "Investigating the Polygenic Relationship Between Cannabis Use and Schizophrenia in the All of Us Research Program.." medRxiv : the preprint server for health sciences, 2025. https://doi.org/10.1101/2025.05.20.25327979
RethinkTHC
RethinkTHC Research Database. "Investigating the Polygenic Relationship Between Cannabis Us..." RTHC-05977. Retrieved from https://rethinkthc.com/research/austin-zimmerman-2025-investigating-the-polygenic-relationship-2
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkTHC research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.