Abstract
Cannabis is widely used worldwide, yet its links to health outcomes are not fully understood. DNA methylation can serve as a mediator to link environmental exposures to health outcomes. We conducted an epigenome-wide association study (EWAS) of peripheral blood-based DNA methylation and lifetime cannabis use (ever vs. never) in a meta-analysis including 9436 participants (7795 European and 1641 African ancestry) from seven cohorts. Accounting for effects of cigarette smoking, our trans-ancestry EWAS meta-analysis revealed four CpG sites significantly associated with lifetime cannabis use at a false discovery rate of 0.05 (p< 5.85 × 10 − 7) : cg22572071 near gene ADGRF1, cg15280358 in ADAM12, cg00813162 in ACTN1, and cg01101459 near LINC01132. Additionally, our EWAS analysis in participants who never smoked cigarettes identified another epigenome-wide significant CpG site, cg14237301 annotated to APOBR. We used a leave-one-out approach to evaluate methylation scores constructed as a weighted sum of the significant CpGs. The best model can explain 3.79% of the variance in lifetime cannabis use. These findings unravel the DNA methylation changes associated with lifetime cannabis use that are independent of cigarette smoking and may serve as a starting point for further research on the mechanisms through which cannabis exposure impacts health outcomes.
Original language | English |
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Pages (from-to) | 124-133 |
Journal | Molecular Psychiatry |
Volume | 29 |
Issue number | 1 |
DOIs | |
Publication status | Published - Jan 2024 |
Bibliographical note
Funding Information:This work was mainly supported by National Institute on Drug Abuse grant number R01DA048824 (PI: Fang). We also acknowledge the contributions of the staff and participants of all cohorts involved in this study, and cohort-specific funding and acknowledgement are included in Supplementary Section.
Publisher Copyright:
© 2023, The Author(s).
Funding
This work was mainly supported by National Institute on Drug Abuse grant number R01DA048824 (PI: Fang). We also acknowledge the contributions of the staff and participants of all cohorts involved in this study, and cohort-specific funding and acknowledgement are included in Supplementary Section.
Funders | Funder number |
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National Institute on Drug Abuse | R01DA048824 |
National Institute on Drug Abuse |
Cohort Studies
- Netherlands Twin Register (NTR)