Epigenome-wide association meta-analysis of DNA methylation with coffee and tea consumption

Irma Karabegović, Eliana Portilla-Fernandez, Yang Li, Jiantao Ma, Silvana C.E. Maas, Daokun Sun, Emily A. Hu, Brigitte Kühnel, Yan Zhang, Srikant Ambatipudi, Giovanni Fiorito, Jian Huang, Juan E. Castillo-Fernandez, Kerri L. Wiggins, Niek de Klein, Sara Grioni, Brenton R. Swenson, Silvia Polidoro, Jorien L. Treur, Cyrille CueninPei Chien Tsai, Ricardo Costeira, Veronique Chajes, Kim Braun, Niek Verweij, Anja Kretschmer, Lude Franke, Joyce B.J. van Meurs, André G. Uitterlinden, Robert J. de Knegt, M. Arfan Ikram, Abbas Dehghan, Annette Peters, Ben Schöttker, Sina A. Gharib, Nona Sotoodehnia, Jordana T. Bell, Paul Elliott, Paolo Vineis, Caroline Relton, Zdenko Herceg, Hermann Brenner, Melanie Waldenberger, Casey M. Rebholz, Trudy Voortman, Qiuwei Pan, Myriam Fornage, Daniel Levy, Manfred Kayser, Mohsen Ghanbari*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

30 Citations (Scopus)


Coffee and tea are extensively consumed beverages worldwide which have received considerable attention regarding health. Intake of these beverages is consistently linked to, among others, reduced risk of diabetes and liver diseases; however, the mechanisms of action remain elusive. Epigenetics is suggested as a mechanism mediating the effects of dietary and lifestyle factors on disease onset. Here we report the results from epigenome-wide association studies (EWAS) on coffee and tea consumption in 15,789 participants of European and African-American ancestries from 15 cohorts. EWAS meta-analysis of coffee consumption reveals 11 CpGs surpassing the epigenome-wide significance threshold (P-value <1.1×10−7), which annotated to the AHRR, F2RL3, FLJ43663, HDAC4, GFI1 and PHGDH genes. Among them, cg14476101 is significantly associated with expression of the PHGDH and risk of fatty liver disease. Knockdown of PHGDH expression in liver cells shows a correlation with expression levels of genes associated with circulating lipids, suggesting a role of PHGDH in hepatic-lipid metabolism. EWAS meta-analysis on tea consumption reveals no significant association, only two CpGs annotated to CACNA1A and PRDM16 genes show suggestive association (P-value <5.0×10−6). These findings indicate that coffee-associated changes in DNA methylation levels may explain the mechanism of action of coffee consumption in conferring risk of diseases.

Original languageEnglish
Article number2830
JournalNature Communications
Issue number1
Publication statusPublished - 14 May 2021

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