Large epigenome study identified DNA methylation changes from cannabis use that are independent of cigarette smoking
A meta-analysis of 9,436 participants across seven cohorts and two ancestries identified four DNA methylation sites significantly associated with lifetime cannabis use after accounting for cigarette smoking effects.
Quick Facts
What This Study Found
Four CpG sites were significantly associated with lifetime cannabis use independent of smoking: cg22572071 (near ADGRF1), cg15280358 (in ADAM12), cg00813162 (in ACTN1), and cg01101459 (near LINC01132). In never-smokers, an additional site was found (cg14237301 in APOBR). A methylation score from these sites explained 3.79% of the variance in lifetime cannabis use.
Key Numbers
9,436 participants (7,795 European, 1,641 African ancestry). 4 significant CpG sites after FDR correction (p < 5.85 x 10^-7). 1 additional site in never-smokers. Methylation score explained 3.79% of variance in lifetime cannabis use.
How They Did This
Trans-ancestry epigenome-wide association study (EWAS) meta-analysis across seven cohorts including 7,795 European and 1,641 African ancestry participants. Analyses controlled for cigarette smoking effects. Leave-one-out approach for methylation score validation.
Why This Research Matters
Separating cannabis-specific epigenetic effects from smoking effects has been a major challenge. This large multi-ethnic study identifies methylation changes attributable to cannabis itself, which could serve as biomarkers and starting points for understanding how cannabis affects health at the molecular level.
The Bigger Picture
These cannabis-specific DNA methylation changes could serve as objective biomarkers for cannabis exposure in research settings and may help explain biological pathways through which cannabis affects health outcomes differently from tobacco.
What This Study Doesn't Tell Us
Peripheral blood methylation may not reflect brain or lung tissue changes. Binary outcome (ever vs never use) does not capture dose or frequency. Cross-sectional design cannot determine whether methylation changes are cause or consequence of use. 3.79% variance explained is modest.
Questions This Raises
- ?What biological functions do the identified genes (ADGRF1, ADAM12, ACTN1) serve, and could their methylation changes explain specific health outcomes?
- ?Do these methylation changes reverse after stopping cannabis use?
Trust & Context
- Key Stat:
- 4 cannabis-specific DNA methylation sites identified across 9,436 participants
- Evidence Grade:
- Large multi-cohort meta-analysis with trans-ancestry replication and careful smoking adjustment. Strong methodology for epigenetic research.
- Study Age:
- 2024 study
- Original Title:
- Trans-ancestry epigenome-wide association meta-analysis of DNA methylation with lifetime cannabis use.
- Published In:
- Molecular psychiatry, 29(1), 124-133 (2024)
- Authors:
- Fang, Fang(2), Quach, Bryan, Lawrence, Kaitlyn G, van Dongen, Jenny, Marks, Jesse A, Lundgren, Sara, Lin, Mingkuan, Odintsova, Veronika V, Costeira, Ricardo, Xu, Zongli, Zhou, Linran, Mandal, Meisha, Xia, Yujing, Vink, Jacqueline M, Bierut, Laura J, Ollikainen, Miina, Taylor, Jack A, Bell, Jordana T, Kaprio, Jaakko, Boomsma, Dorret I, Xu, Ke, Sandler, Dale P, Hancock, Dana B, Johnson, Eric O
- Database ID:
- RTHC-05302
Evidence Hierarchy
Watches what happens naturally without intervening.
What do these levels mean? →Frequently Asked Questions
What does DNA methylation mean for health?
DNA methylation is a chemical tag that can turn genes on or off without changing the DNA sequence. Changes in methylation from cannabis use could alter how genes function, potentially affecting health, though the specific consequences of these four sites are not yet known.
Could this be used as a drug test?
The methylation score explained only 3.79% of variance in cannabis use, making it far too imprecise for individual testing. It is more useful as a research tool to study population-level biological effects of cannabis.
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Cite This Study
https://rethinkthc.com/research/RTHC-05302APA
Fang, Fang; Quach, Bryan; Lawrence, Kaitlyn G; van Dongen, Jenny; Marks, Jesse A; Lundgren, Sara; Lin, Mingkuan; Odintsova, Veronika V; Costeira, Ricardo; Xu, Zongli; Zhou, Linran; Mandal, Meisha; Xia, Yujing; Vink, Jacqueline M; Bierut, Laura J; Ollikainen, Miina; Taylor, Jack A; Bell, Jordana T; Kaprio, Jaakko; Boomsma, Dorret I; Xu, Ke; Sandler, Dale P; Hancock, Dana B; Johnson, Eric O. (2024). Trans-ancestry epigenome-wide association meta-analysis of DNA methylation with lifetime cannabis use.. Molecular psychiatry, 29(1), 124-133. https://doi.org/10.1038/s41380-023-02310-w
MLA
Fang, Fang, et al. "Trans-ancestry epigenome-wide association meta-analysis of DNA methylation with lifetime cannabis use.." Molecular psychiatry, 2024. https://doi.org/10.1038/s41380-023-02310-w
RethinkTHC
RethinkTHC Research Database. "Trans-ancestry epigenome-wide association meta-analysis of D..." RTHC-05302. Retrieved from https://rethinkthc.com/research/fang-2024-transancestry-epigenomewide-association-metaanalysis
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.