Do not risk missing a new paper describing a recent trans-ancestry epigenome-wide association study (EWAS) highlighting the significant health risks of recreational cannabis! In a fascinating new study, researchers now reveal that cannabis exposure can impact DNA methylation levels at specific regions independent of cigarette smoking to increase the risk of adverse health outcomes.
Risk-averse researchers led by Fang Fang (RTI International) undertook the largest EWAS of peripheral blood-based DNA methylation and lifetime cannabis use in a meta-analysis of data from 9436 participants of European and African ancestry from seven distinct cohorts (representing both sexes and a wide range of ages) in the hope of deepening our understanding of any links between drug exposure and adverse health outcomes. While previous EWAS reports identified DNA methylation differences following cannabis use (the Fang group and others), in-depth knowledge of specific changes remained somewhat limited; now, these new findings may fully explain how cannabis use increases the risk of adverse health outcomes.
Let’s hear from Fang and colleagues on how they revealed the epigenetic risks of cannabis exposure:
- An initial basic model adjusted for sex, age, blood cell proportions, and technical covariates yields over 600 significant CpGs, with 82% overlapping with prior EWAS findings for cigarette smoking
- Overall, cannabis use and cigarette smoking independently influence DNA methylation at shared CpGs
- After accounting for cigarette smoking, an EWAS meta-analysis reveals four CpG sites statistically independent of cigarette smoking that significantly associate with lifetime cannabis use and whose associated genes possess links to various diseases/disorders
- cg22572071 near ADGRF1; increased methylation – neuroinflammation and breast cancercg15280358 in ADAM12; increased methylation – an emerging prognostic biomarker for cancercg00813162 in ACTN1; decreased methylation – differentially methylated in sperm in cannabis users
- cg01101459 near LINC01132; decreased methylation – long non-coding RNA with oncogenic functions
- An EWAS analysis in participants who never smoked cigarettes eliminates the influence of cigarette smoking and identifies an additional significant CpG site
- cg14237301 annotated to APOBR; decreased methylation – genetic variants associated with lifetime cannabis use
The researchers involved in this study risked nothing; the large sample set employed provides robust, generalizable findings – the identification of specific DNA methylation changes induced by lifetime cannabis use may lead to adverse health outcomes. The authors next hope to integrate cannabis use patterns, genome-wide association study results, DNA methylation data from multiple tissues (such as the brain), and gene expression data to next describe causal links between cannabis use and DNA methylation levels.
For more on the risks of lifetime recreational cannabis use, see Molecular Psychiatry, November 2023.