Alcohol consumption and DNA methylation: an epigenome-wide association study within the French E3N cohort

Background: Alcohol consumption can have harmful effects on health, depending on the quantity and frequency. Understanding the underlying molecular mechanisms is essential to grasp its health consequences. The study aimed to assess the association between alcohol consumption and blood DNA methylation, an epigenetic mechanism that controls gene expression. Methods: The epigenome-wide association study (EWAS) included 1,538 women from a case-cohort study within the French E3N cohort. Weighted linear mixed-effects models were used to assess the associations between self-reported alcohol consumption (in g/day in 1993) and DNA methylation at 715,986 CpGs measured with the HumanMethylationEPIC Beadchip. Women were cancer-free at blood collection in 1995–1999. Results: Of the 715,986 sites analyzed, 19,255 were associated with alcohol consumption (FDR < 0.05). Over-representation analysis highlighted enrichment of genes involved in cancer, the nervous system and aging. Of these 19,255 sites, 1,528 were replicated in an independent case–control study, with 85 also identified in other EWAS. Notably, at least six studies reported sites in SLC7A11, ANP32B, MCM2, HNRNPA1, SNORD30, and TRA2B genes. Conclusions: Several potential methylation markers for alcohol consumption, documented prior to blood sampling, have been identified. The link between these sites and chronic diseases should be investigated to understand the molecular mechanisms underlying the harmful effects of alcohol consumption on health.