Impact of tobacco, alcohol, and marijuana on genome-wide DNA methylation and its relationship with hypertension
Carreras-Gallo, Natàlia (Barcelona Institute for Global Health (ISGlobal))
Dwaraka, Varun B. (TruDiagnostic)
Cáceres, Alejandro (Universitat Politècnica de Catalunya)
Smith, Ryan (TruDiagnostic)
Mendez, Tavis L. (TruDiagnostic)
Went, Hannah (TruDiagnostic)
González, Juan Ramón (Universitat Autònoma de Barcelona. Departament de Matemàtiques)

Date:	2023
Abstract:	Tobacco, alcohol, and marijuana consumption is an important public health problem because of their high use worldwide and their association with the risk of mortality and many health conditions, such as hypertension, which is the commonest risk factor for death throughout the world. A likely pathway of action of substance consumption leading to persistent hypertension is DNA methylation. Here, we evaluated the effects of tobacco, alcohol, and marijuana on DNA methylation in the same cohort (N = 3,424). Three epigenome-wide association studies (EWAS) were assessed in whole blood using the InfiniumHumanMethylationEPIC BeadChip. We also evaluated the mediation of the top CpG sites in the association between substance consumption and hypertension. Our analyses showed 2,569 CpG sites differentially methylated by alcohol drinking and 528 by tobacco smoking. We did not find significant associations with marijuana consumption after correcting for multiple comparisons. We found 61 genes overlapping between alcohol and tobacco that were enriched in biological processes involved in the nervous and cardiovascular systems. In the mediation analysis, we found 66 CpG sites that significantly mediated the effect of alcohol consumption on hypertension. The top alcohol-related CpG site (cg06690548, P-value = 5. 9·10 −83) mapped to SLC7A11 strongly mediated 70. 5% of the effect of alcohol consumption on hypertension (P-value = 0. 006). Our findings suggest that DNA methylation should be considered for new targets in hypertension prevention and management, particularly concerning alcohol consumption. Our data also encourage further research into the use of methylation in blood to study the neurological and cardiovascular effects of substance consumption.
Grants:	Ministerio de Ciencia e Innovación CEX2018-000806-S
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Tobacco ; Alcohol ; Marijuana ; DNA methylation ; Epigenome-wide association study ; Hypertension
Published in:	Epigenetics, Vol. 18, Issue 1 (May 2023) , art. 2214392, ISSN 1559-2308

DOI: 10.1080/15592294.2023.2214392
PMID: 37216580

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