Meta-analysis of Cannabis Use Identifies Shared Genetic Loci with Sleep and Circadian Rhythms

May 1, 2026medRxiv : the preprint server for health sciences

Shared Genetic Links Between Cannabis Use and Sleep and Body Clock Patterns

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Abstract

A meta-analysis of 373,079 participants identified 39 independent genetic loci associated with cannabis use.

Significant positive genetic correlations were found between cannabis use and clinical insomnia, as well as insomnia-related medication usage.
Negative correlations were observed with morningness chronotype and daytime activity.
The genetic architecture of cannabis use shows heavy enrichment in the central nervous system and specific brain cell types.
Fine-mapping and colocalization analyses indicated shared genetic signals between cannabis use and clinical insomnia.

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Cannabis use is an increasingly common therapeutic for a variety of chronic diseases. In addition, people with sleep problems may self-medicate using cannabis products. However, genetic architecture of cannabis use and its shared genetic predispositions with sleep traits has not been systematically examined. We performed a meta-analysis of cannabis use within the All of Us and UK Biobank cohorts, consisting of 152,807 cases and 220,272 controls. Our meta-analysis identified 39 independent loci, including the previously reportedlocus associated with cannabis use and replicating previous work. Additionally our associations include neuronal and sleep-regulating genes such as, and. Moreover, tissue-specific analyses revealed that the genetic architecture of cannabis use is heavily enriched within the central nervous system and specific brain cell types. In addition, we observed significant positive genetic correlations with clinical insomnia, insomnia-related medication usage, and objectively measured nighttime physical activity, alongside negative correlations with morningness chronotype and daytime activity. Fine-mapping and colocalization analyses identified shared genetic signals between cannabis use and clinical insomnia including a near-perfect colocalization atand. Together, these results highlight the shared genetic risk between cannabis use and sleep disorders. Additionally, our findings indicate the importance of investigating the genetic effects of cannabis use as its use becomes more widespread, both recreationally and medicinally. CADM2HTR1A, RAI1, SLC39A8NCAM1SLC39A8CADM2

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Meta-analysis of Cannabis Use Identifies Shared Genetic Loci with Sleep and Circadian Rhythms

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