Alcohol and tobacco changed thousands of DNA methylation sites, but marijuana showed no significant effects | Research

The takeaway

In a cohort of 3,424 adults, alcohol drinking altered 2,569 DNA methylation sites and tobacco smoking altered 528, but marijuana consumption showed no significant methylation changes after correcting for multiple comparisons.

Epigenetics researchers, cardiovascular risk researchers, substance use epidemiologists

Marijuana: 0 significant methylation changes vs. 2,569 for alcohol

What the researchers found

Three epigenome-wide association studies in the same cohort found 2,569 CpG sites differentially methylated by alcohol and 528 by tobacco. Marijuana showed no significant associations after multiple comparison correction. Sixty-one genes overlapped between alcohol and tobacco, enriched in nervous and cardiovascular system processes. Sixty-six CpG sites mediated alcohol's effect on hypertension, with the top site (SLC7A11) mediating 70.5% of the effect.

Why it matters

This is one of the first studies to compare epigenetic effects of all three substances in the same cohort, providing an important null result for marijuana while revealing that alcohol may drive hypertension largely through DNA methylation changes.

The numbers in context

3,424 participants; 2,569 CpG sites for alcohol; 528 for tobacco; 0 significant for marijuana; 61 overlapping genes; 66 CpG sites mediated alcohol-hypertension link; SLC7A11 mediated 70.5% of alcohol's hypertension effect (P=0.006)

How the study worked

Epigenome-wide association studies using the Infinium EPIC BeadChip in whole blood from 3,424 participants. Assessed effects of tobacco, alcohol, and marijuana on DNA methylation, followed by mediation analysis for hypertension.

What this study cannot tell us

Cross-sectional design cannot establish temporal relationships. Marijuana use may have been less prevalent or at lower levels than alcohol/tobacco in this cohort. Blood-based methylation may not reflect tissue-specific effects. Multiple comparison correction may have been overly conservative for marijuana given lower statistical power.

How to read the evidence

Well-powered epigenome-wide study using validated methylation array in a single cohort, though cross-sectional design and potential power limitations for marijuana analysis are caveats.

When this study was published

Published 2023

The bigger picture

The finding that alcohol and tobacco produce extensive epigenetic changes while marijuana does not provides molecular-level context for the relative health impacts of these three commonly used substances.

Questions still open

Would higher-dose or longer-duration marijuana use produce detectable methylation changes? Are the null marijuana findings due to truly no effect or insufficient power?

Common questions

Does marijuana change DNA methylation like alcohol and tobacco do?

In this study of 3,424 adults, alcohol altered 2,569 DNA sites and tobacco 528, but marijuana showed no significant changes after statistical correction, suggesting a different epigenetic impact profile.

How does alcohol affect hypertension through DNA changes?

The study found 66 DNA methylation sites that mediated alcohol's effect on hypertension, with the top site in the SLC7A11 gene accounting for 70.5% of alcohol's contribution to hypertension risk.

Read the original research

Impact of tobacco, alcohol, and marijuana on genome-wide DNA methylation and its relationship with hypertension.

Epigenetics, 18(1), 2214392

View on PubMed ↗Publisher’s paper ↗

Citation

Carreras-Gallo, Natàlia; Dwaraka, Varun B; Cáceres, Alejandro; Smith, Ryan; Mendez, Tavis L; Went, Hannah; Gonzalez, Juan R. (2023). Impact of tobacco, alcohol, and marijuana on genome-wide DNA methylation and its relationship with hypertension.. Epigenetics, 18(1), 2214392. https://doi.org/10.1080/15592294.2023.2214392