Coffee, Tea, and CpG: Do beverages affect DNA Methylation

Epigenetics can mediate the effects of dietary and lifestyle factors on disease onset, and two previous epigenome-wide association studies (EWAS) reported the association of DNA methylation status at certain CpGs with tea or coffee consumption (Ek et al. and Chuang et al.); however, these studies employed modest sample sizes. To solve this problem and fully establish a strong link between coffee and tea consumption and human disease risk, researchers headed by Mohsen Ghanbari (Erasmus University Medical Center, Rotterdam, Netherlands) undertook a large-scale EWAS meta-analysis of blood samples isolated from around 16,000 middle-aged and elderly European and African American individuals from fifteen different cohorts.

Karabegović and colleagues first described how their meta-analysis of coffee consumption revealed significant associations with differential DNA methylation of peripheral blood-derived DNA at eleven CpGs. Overall, high coffee intake correlated with lower methylation at CpGs annotated to the AHRR gene, which forms part of the xenobiotic metabolism pathway, and the F2RL3, GFI1, and IER3 genes, which are involved in a range of phenotypes, including inflammatory responses, cancer, and cardio-metabolic diseases. High coffee intake also induced the opposite effect at specific sites, inducing higher methylation at CpGs that annotated to the LINC-PINT gene, which currently lacks any reported links with disease predisposition, and the HDAC4 gene, which encodes a histone deacetylase involved in cocaine-related behaviors (Penrod et al. and Kumar et al.).

Additionally, one CpG sites (cg14476101; Whal et al.) with coffee-associated differential-methylation significantly associated with PHGDH (encoding phosphoglycerate dehydrogenase) gene expression and fatty liver disease risk (Ma et al.). These findings, combined with those of earlier EWAS, indicate that coffee intake alters PHGDH gene expression and liver function by altering the methylation of cg14476101. Interestingly, PHGDH knockdown in liver cells altered the expression of lipid-associated genes (decreased LPL and increased LDLR and ABCA1), suggesting that the regulation of PHGDH expression impacts lipid metabolism in the liver.

Unfortunately, the meta-analysis of tea consumption failed to reveal any significant associations, although two CpGs associated with the CACNA1A and PRDM16 (encoding a histone methyltransferase) genes displayed nominal associations. Compared with coffee, the lack of statistically significant associations compared to tea consumption may derive from the presence/higher abundance of specific nutrients only in coffee, such as caffeine or various phenolic compounds (Temple et al.).

Overall, this study suggests that coffee beats tea when altering DNA methylation levels at specific CpGs to modify disease risk. The large sample size and multi-ethnic contribution and the incorporation of different adjustment models to limit confounding represented the significant strengths of this study; however, the authors also note some limitations, such as a residual confounding effect of smoking (Joehanes et al.) (heavier smokers tend to drink more coffee (Bjørngaard et al.)) and the absence of age groups other than middle-aged and elderly individuals, which they aimed to address in their continuing research. They also noted the need to further explore the biological relevance of the associated DNA methylation sites and genes concerning different health outcomes.

For more on how coffee and tea may impact your DNA methylation profile to influence disease risk, see Nature Communications, May 2021.