DOI: 10.6084/m9.figshare.23065060
title: Impact of tobacco, alcohol, and marijuana on genome-wide DNA methylation and its relationship with hypertension

description: 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 (<i>N</i> = 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<sup>−83</sup>) 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. The consumption of tobacco, alcohol, and marijuana is very high worldwide and is associated with common diseases, like cardiovascular and neurological disorders.This study found that tobacco and alcohol have large effects on genome wide DNA methylation while marijuana consumption has nonsignificant effects.The genes differentially methylated were enriched in pathways related to neurodevelopment, suggesting the mediation between recreational drug consumption and neurological disorders.More remarkably, 66 alcohol related CpG sites significantly mediated the association between heavy drinking and hypertension.Our findings suggest that DNA methylation changes should be considered for new targets in disease prevention for recreational drug consumers. The consumption of tobacco, alcohol, and marijuana is very high worldwide and is associated with common diseases, like cardiovascular and neurological disorders. This study found that tobacco and alcohol have large effects on genome wide DNA methylation while marijuana consumption has nonsignificant effects. The genes differentially methylated were enriched in pathways related to neurodevelopment, suggesting the mediation between recreational drug consumption and neurological disorders. More remarkably, 66 alcohol related CpG sites significantly mediated the association between heavy drinking and hypertension. Our findings suggest that DNA methylation changes should be considered for new targets in disease prevention for recreational drug consumers.