Trans-ancestry epigenome-wide association meta-analysis of DNA methylation with lifetime cannabis use

Fang Fang*, Bryan Quach, Kaitlyn G. Lawrence, Jenny van Dongen, Jesse A. Marks, Sara Lundgren, Mingkuan Lin, Veronika V. Odintsova, Ricardo Costeira, Zongli Xu, Linran Zhou, Meisha Mandal, Yujing Xia, Jacqueline M. Vink, Laura J. Bierut, Miina Ollikainen, Jack A. Taylor, Jordana T. Bell, Jaakko Kaprio, Dorret I. BoomsmaKe Xu, Dale P. Sandler, Dana B. Hancock, Eric O. Johnson

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review

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 languageEnglish
Pages (from-to)124-133
JournalMolecular Psychiatry
Volume29
Issue number1
DOIs
Publication statusPublished - 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.

FundersFunder number
National Institute on Drug AbuseR01DA048824
National Institute on Drug Abuse

    Cohort Studies

    • Netherlands Twin Register (NTR)

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