학술논문
Trans-ancestry epigenome-wide association meta-analysis of DNA methylation with lifetime cannabis use
Document Type
Article
Author
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.
Source
Molecular Psychiatry; January 2024, Vol. 29 Issue: 1 p124-133, 10p
Subject
Language
ISSN
13594184; 14765578
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.