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

Irma Karabegović, et al.

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Received Date: 15th April 20

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 Cuenin, Pei-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

Coffee and tea are extensively consumed beverages worldwide. Observational studies have shown contradictory findings for the association between consumption of these beverages and different health outcomes. Epigenetics is suggested as a mechanism mediating the effects of dietary and lifestyle factors on disease onset. We conducted epigenome-wide association studies (EWAS) on coffee and tea consumptions in 15,789 participants of European and African-American ancestries from 15 cohorts. EWAS meta-analysis revealed 11 CpG sites significantly associated with coffee consumption (P-value<1.1×10-7), nine of them annotated to the genes AHRR, F2RL3, FLJ43663, HDAC4, GFI1 and PHGDH, and two CpGs suggestively associated with tea consumption (P-value<5.0×10-6). Among these, cg14476101 was significantly associated with expression of its annotated gene PHGDH and risk of fatty liver disease. Knockdown of PHGDH expression in liver cells showed a correlation with expression levels of lipid-associated genes, suggesting a role of PHGDH in hepatic-lipid metabolism. Collectively, this study indicates that coffee consumption is associated with differential DNA methylation levels at multiple CpGs, and that coffee-associated epigenetic variations may explain the mechanism of action of coffee consumption in conferring disease risk.

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This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.

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