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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 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, View ORCID ProfileMohsen Ghanbari
doi: https://doi.org/10.1101/2020.04.15.042267
Irma Karabegović
1Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands
2Department of Genetic Identification, Erasmus University Medical Center, Rotterdam, the Netherlands
3Epidemiology and Microbial Genomics, National Health Laboratory, L-3555 Dudelange, Luxembourg
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Eliana Portilla-Fernandez
1Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands
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Yang Li
4Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, the Netherlands
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Jiantao Ma
5Friedman School of Nutrition Science and Policy, Tufts University, Boston, Massachusetts, USA
6Population Sciences Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland and the Framingham Heart Study, Framingham, Massachusetts, USA
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Silvana C.E. Maas
1Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands
2Department of Genetic Identification, Erasmus University Medical Center, Rotterdam, the Netherlands
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Daokun Sun
7Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, 1825 Pressler Street, Houston, Texas, USA 77030
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Emily A. Hu
8Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe - Street, Baltimore, Maryland, USA 21205
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Brigitte Kühnel
9Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, D-85764, Neuherberg, Germany
10Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, D-85764, Neuherberg, Germany
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Yan Zhang
11Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
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Srikant Ambatipudi
12MRC Integrative Epidemiology Unit, Population Health Sciences, University of Bristol, Bristol, BS8 2BN, UK
13AMCHSS, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala, India
14Epigenetics Group, International Agency for Research on Cancer (IARC), 69372 Lyon Cedex 08, France
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Giovanni Fiorito
15Laboratory of Biostatistics, Department of Biomedical Sciences, University of Sassari, Italy
16MRC Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, St Mary’s Campus, Imperial College London, Norfolk Place, London W2 1PG, UK
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Jian Huang
16MRC Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, St Mary’s Campus, Imperial College London, Norfolk Place, London W2 1PG, UK
17UK Dementia Research Institute at Imperial College London, London, UK
18Imperial College NIHR Biomedical Research Centre, London, UK
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Juan E. Castillo-Fernandez
19Department of Twin Research and Genetic Epidemiology, Kings College London, London, SE1 7EH, UK
20Epigenetics Programme, Babraham Institute, Cambridge, UK
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Kerri L. Wiggins
21Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle CHRU, 1730 Minor Ave, Suite 1360, Seattle, WA 98101, USA
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Niek de Klein
22Department of Genetics, University Medical Center Groningen, University of Groningen, Hanzeplein 1, Groningen, The Netherlands
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Sara Grioni
23Epidemiology and Prevention Unit, IRCCS National Cancer Institute Foundation, Milan, Italy
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Brenton R. Swenson
21Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle CHRU, 1730 Minor Ave, Suite 1360, Seattle, WA 98101, USA
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Silvia Polidoro
24Italian Institute for Genomic Medicine (IIGM, former HuGeF), c/o IRCCS Candiolo, SP142, km 3,95 – 10060 Candiolo
16MRC Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, St Mary’s Campus, Imperial College London, Norfolk Place, London W2 1PG, UK
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Jorien L. Treur
25Department of Psychiatry, Amsterdam UMC, Amsterdam, the Netherlands
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Cyrille Cuenin
14Epigenetics Group, International Agency for Research on Cancer (IARC), 69372 Lyon Cedex 08, France
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Pei-Chien Tsai
19Department of Twin Research and Genetic Epidemiology, Kings College London, London, SE1 7EH, UK
26Department of Biomedical Sciences, Chang Gung University, Taoyuan, Taiwan
27Genomic Medicine Research Core Laboratory, Chang Gung Memorial Hospital, Linkou, Taiwan
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Ricardo Costeira
19Department of Twin Research and Genetic Epidemiology, Kings College London, London, SE1 7EH, UK
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Veronique Chajes
28Nutritional Epidemiology Group, International Agency for Research on Cancer, 69373 Lyon, France
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Kim Braun
1Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands
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Niek Verweij
22Department of Genetics, University Medical Center Groningen, University of Groningen, Hanzeplein 1, Groningen, The Netherlands
29Genomics plc, Park End St, Oxford, UK
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Anja Kretschmer
9Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, D-85764, Neuherberg, Germany
10Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, D-85764, Neuherberg, Germany
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Lude Franke
22Department of Genetics, University Medical Center Groningen, University of Groningen, Hanzeplein 1, Groningen, The Netherlands
30Oncode Institute, Utrecht, The Netherlands
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Joyce B.J. van Meurs
31Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands
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André G. Uitterlinden
31Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands
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Robert J. de Knegt
4Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, the Netherlands
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M. Arfan Ikram
1Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands
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Abbas Dehghan
16MRC Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, St Mary’s Campus, Imperial College London, Norfolk Place, London W2 1PG, UK
17UK Dementia Research Institute at Imperial College London, London, UK
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Annette Peters
9Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, D-85764, Neuherberg, Germany
10Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, D-85764, Neuherberg, Germany
32German Center for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany
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Ben Schöttker
11Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
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Sina A. Gharib
33Computational Medicine Core at Center for Lung Biology, Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington, 850 Republican Street, Seattle, WA, 98109, USA
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Nona Sotoodehnia
21Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle CHRU, 1730 Minor Ave, Suite 1360, Seattle, WA 98101, USA
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Jordana T. Bell
19Department of Twin Research and Genetic Epidemiology, Kings College London, London, SE1 7EH, UK
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Paul Elliott
16MRC Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, St Mary’s Campus, Imperial College London, Norfolk Place, London W2 1PG, UK
17UK Dementia Research Institute at Imperial College London, London, UK
18Imperial College NIHR Biomedical Research Centre, London, UK
34Health Data Research UK-London, London, UK
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Paolo Vineis
16MRC Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, St Mary’s Campus, Imperial College London, Norfolk Place, London W2 1PG, UK
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Caroline Relton
12MRC Integrative Epidemiology Unit, Population Health Sciences, University of Bristol, Bristol, BS8 2BN, UK
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Zdenko Herceg
14Epigenetics Group, International Agency for Research on Cancer (IARC), 69372 Lyon Cedex 08, France
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Hermann Brenner
11Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
35Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany
36German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
37Network Aging Research, University of Heidelberg, Heidelberg, Germany
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Melanie Waldenberger
9Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, D-85764, Neuherberg, Germany
10Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, D-85764, Neuherberg, Germany
32German Center for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany
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Casey M. Rebholz
8Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe - Street, Baltimore, Maryland, USA 21205
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Trudy Voortman
1Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands
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Qiuwei Pan
4Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, the Netherlands
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Myriam Fornage
7Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, 1825 Pressler Street, Houston, Texas, USA 77030
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Daniel Levy
6Population Sciences Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland and the Framingham Heart Study, Framingham, Massachusetts, USA
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Manfred Kayser
2Department of Genetic Identification, Erasmus University Medical Center, Rotterdam, the Netherlands
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Mohsen Ghanbari
1Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands
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  • ORCID record for Mohsen Ghanbari
  • For correspondence: m.ghanbari@erasmusmc.nl
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Abstract

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.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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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 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
bioRxiv 2020.04.15.042267; doi: https://doi.org/10.1101/2020.04.15.042267
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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 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
bioRxiv 2020.04.15.042267; doi: https://doi.org/10.1101/2020.04.15.042267

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