Genome-wide DNA methylation analysis of heavy cannabis exposure in a New Zealand longitudinal cohort
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Abstract
Cannabis use is of increasing public health interest globally. Here we examined the effect of heavy cannabis use, with and without tobacco, on genome-wide DNA methylation in a longitudinal birth cohort (Christchurch Health and Development Study, CHDS). A total of 48 heavy cannabis users were selected from the CHDS cohort, on the basis of their adult exposure to cannabis and tobacco, and DNA methylation assessed from whole blood samples, collected at approximately age 28. Methylation in heavy cannabis users was assessed, relative to non-users ( n = 48 controls) via the Illumina Infinium® MethylationEPIC BeadChip. We found the most differentially methylated sites in cannabis with tobacco users were in the AHRR and F2RL3 genes, replicating previous studies on the effects of tobacco. Cannabis-only users had no evidence of differential methylation in these genes, or at any other loci at the epigenome-wide significance level ( P < 10 −7 ). However, there were 521 sites differentially methylated at P < 0.001 which were enriched for genes involved in neuronal signalling (glutamatergic synapse and long-term potentiation) and cardiomyopathy. Further, the most differentially methylated loci were associated with genes with reported roles in brain function (e.g. TMEM190 , MUC3L , CDC20 and SP9 ). We conclude that the effects of cannabis use on the mature human blood methylome differ from, and are less pronounced than, the effects of tobacco use, and that larger sample sizes are required to investigate this further.
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Within the sample of cannabis users without tobacco, none of the differentially methylated loci reached EWAS significance, but an exploratory analysis showed enrichment for genes involved in the signalling pathway, including glutamatergic transmission, brain function and mood disorders.
“Within the sample of cannabis users without tobacco, while none of the differentially methylated loci reached EWAS significance, an exploratory analysis showed enrichment for genes involved in the signalling pathway, including glutamatergic transmission, brain function and mood disorders.”
From Can epigenetics shine a light on the biological pathways underlying major mental disorders? (2022) · cites this paper as Osborne et al., 2020
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Experimental — accuracy not yet measuredExploratory analyses show two differentially methylated sites significantly associated with both only cannabis use and cannabis with tobacco, which are within the MARC2 gene and within the CUX1 gene.
“Moreover, these exploratory analyses show two differentially methylated sites significantly associated with both only CU and cannabis with tobacco, which are within the MARC2 gene. The latter previously linked to adverse effects to antipsychotics in schizophrenia (Åberg et al., 2010) and within the CUX1 gene which is involved in neuronal development (Platzer et al., 2018).”
From Can epigenetics shine a light on the biological pathways underlying major mental disorders? (2022) · cites this paper as Osborne et al., 2020
The Discussion identifies two overlapping CpG sites in MARC2 and CUX1 in the cannabis-only and cannabis-with-tobacco analyses. It calls them only nominally significant (P < 0.05), while the Results report that no cannabis-only sites remained significant after correction for multiple testing. The claim omits that important qualification. (LLM, conf=0.88)
Experimental — accuracy not yet measuredIn a sample with both cannabis and tobacco use, analyses identified differentially methylated sites in 2 genes, AHRR and F2RL, previously reported to be affected by tobacco exposure.
“The analyses in the sample with both cannabis and tobacco use identified differentially methylated sites in 2 genes, AHRR and F2RL, previously reported to be affected by tobacco exposure.”
From Can epigenetics shine a light on the biological pathways underlying major mental disorders? (2022) · cites this paper as Osborne et al., 2020
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- Authors
- Osborne, A. J., Pearson, J. F., Noble, A. J., Gemmell, N. J., Horwood, L. J., Boden, J. M., Benton, M. C., Macartney-Coxson, D. P., & Kennedy, M. A.
- Affiliations
- University of Canterbury (NZ)
- University of Otago (NZ)
- New Zealand Institute for Public Health and Forensic Science (NZ)
- Corresponding author
- Osborne, Amy J.
- Kennedy, Martin A.
- ORCID
- Venue
- Translational Psychiatry
- Published
- 2020-04-22
- Volume
- 10
- Issue
- 1
- Pages
- 114-114
- ISSN
- 2158-3188 (ISSN-L)
- PMC
- PMC7176736
- OpenAlex
- W3018202073
- Cited by
- 47
- References
- 112
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 7 · 2023: 11 · 2022: 8 · 2021: 11 · 2020: 1
- FWCI
- 2.51
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Translational Psychiatry (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- University of Canterbury Research Repository (University of Canterbury) (submittedVersion)
- Funders
- University of Otago
- Canterbury Medical Research Foundation
- Health Research Council of New Zealand (16-600, Programme Grant 16/600)
- Division of Health Sciences, University of Otago
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Keywords
- heavy cannabis use, DNA methylation, epigenetics, tobacco use, AHRR, F2RL3, neuronal signaling, glutamatergic synapses, long-term potentiation, cardiomyopathy, Christchurch Health and Development Study, birth cohort
- MeSH terms
- Adult, Cannabis, Humans, New Zealand, CpG Islands, DNA Methylation, Epigenesis, Genetic, Genome-Wide Association Study
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