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Alcohol and Tobacco Use Lead to Major Epigenetic Changes

A new study simultaneously assesses the effect of tobacco, alcohol and marijuana on DNA methylation and its relationship to hypertension.


Alcohol and tobacco consumption have a considerable effect on genome methylation, and many of the genes that show methylation differences are involved in neurodevelopment, according to a study led by ISGlobal, an institution supported by "la Caixa" Foundation. The study, carried out on a US cohort, also reveals methylation changes that could explain the association between high alcohol consumption and hypertension.

The consumption of substances such as alcohol, tobacco and marijuana has been associated with neurological and cardiovascular disorders. The mechanisms underlying these associations are not clear, but one possible pathway could be by modulating DNA methylation. This epigenetic change involves the addition of a methyl group at certain sites along the genome, which does not cause changes in the DNA sequence itself, but does affect how much the gene is expressed.  

In this study, ISGlobal researcher Juan Ramón González and his team evaluated the effects of tobacco, alcohol and marijuana on DNA methylation throughout the entire genome, with the idea of identifying metabolic pathways that could be affected and that could explain the association between these substances and neurological and cardiovascular disorders.

The analysis involved DNA samples from 3,590 Americans aged 13 to 97, who answered a series of questions about medical history, family history and lifestyle habits. Alcohol was the most common substance used (2,790 of the 3,590 people), followed by marijuana (367 people) and tobacco (149). About one in seven people reported using more than one drug on certain occasions.

Genes associated with neurodevelopment

The analysis revealed that tobacco and alcohol significantly affect genome methylation (2,569 sites differentially methylated by alcohol, 528 by tobacco). Marijuana use also had effects on methylation, but they were not significant. "We confirmed many of the methylation sites previously described for tobacco, and identified some new ones," explains Natalia Carreras-Gallo, first author of the study. For alcohol, they found altered methylation in genes associated with autistic disorder, scoliosis, depressed nasal bridge, and other features typical of foetal alcohol syndrome.

Many of the genes affected by tobacco were also affected by alcohol, suggesting that these substances have a similar epigenetic impact. In addition, a large percentage of these genes play a role in the development or function of the nervous system.  "Our results suggest that these substances, which are widely consumed worldwide, affect common metabolic pathways that can lead to neurological disorders," says González.

Hypertension and alcohol

Hypertension was linked to smoking (three times the risk for people who smoke 6-10 cigarettes a day) and alcohol (almost twice the risk for those who drink daily). In addition, the team identified several methylation sites that mediated the association between alcohol and hypertension, some of them in genes involved in vascular function. These findings suggest that DNA methylation could be a target for the treatment of hypertension in heavy drinkers.

"Our study also opens the possibility of using methylation biomarkers in blood to detect and monitor addictions to these substances," adds González.



Natàlia Carreras-Gallo, Varun B. Dwaraka, Alejandro Cáceres, Ryan Smith, Tavis L. Mendez, Hannah Went, Juan R González. Impact of tobacco, alcohol, and marijuana on genome-wide DNA methylation and its relationship with hypertension. Epigenetics. May, 2023.