Trans-ancestry epigenome-wide association meta-analysis of DNA methylation with lifetime cannabis use
Trans-ancestry epigenome-wide association meta-analysis of DNA methylation with lifetime cannabis use
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DOI：
10.1038/s41380-023-02310-w
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发表时间：
2023-11-07
影响因子：
11
通讯作者：
Johnson，Eric O.
中科院分区：
文献类型：
--
作者：
Fang，Fang;Quach，Bryan;Johnson，Eric O.
大麻在世界范围内被广泛使用，但其与健康结果的联系尚未得到充分了解。DNA甲基化可以作为一种媒介，将环境暴露与健康结果联系起来。我们在一项荟萃分析中进行了一项基于外周血的DNA甲基化和终生大麻使用（曾经与从未）的表观基因组关联研究（EWAS），包括来自7个队列的9436名参与者（7795名欧洲人和1641名非洲人血统）。考虑到吸烟的影响，我们的跨祖先EWAS荟萃分析显示，4个CpG位点与终生大麻使用显著相关，错误发现率为0.05：基因ADGRF1附近的cg22572071，ADAM 12中的cg15280358，ACTN 1中的cg00813162和LINC01132附近的cg01101459。此外，我们在从不吸烟的参与者中进行的EWAS分析确定了另一个表观基因组显著的CpG位点，cg14237301注释为APOBR。我们使用留一法来评估构建为显著CpG的加权和的甲基化评分。最好的模型可以解释3.79%的终生大麻使用方差。这些发现揭示了与大麻使用无关的DNA甲基化变化，并可能作为进一步研究大麻暴露影响健康结果的机制的起点。
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: cg22572071 near geneADGRF1, cg15280358 inADAM12, cg00813162 inACTN1, and cg01101459 nearLINC01132. Additionally, our EWAS analysis in participants who never smoked cigarettes identified another epigenome-wide significant CpG site, cg14237301 annotated toAPOBR. 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.