DNA methylation signature of chronic low-grade inflammation and its role in cardio-respiratory diseases

Matthias Wielscher (), Pooja R. Mandaviya, Brigitte Kuehnel, Roby Joehanes, Rima Mustafa, Oliver Robinson, Yan Zhang, Barbara Bodinier, Esther Walton, Pashupati P. Mishra, Pascal Schlosser, Rory Wilson, Pei-Chien Tsai, Saranya Palaniswamy, Riccardo E. Marioni, Giovanni Fiorito, Giovanni Cugliari, Ville Karhunen, Mohsen Ghanbari, Bruce M. Psaty, Marie Loh, Joshua C. Bis, Benjamin Lehne, Nona Sotoodehnia, Ian J. Deary, Marc Chadeau-Hyam, Jennifer A. Brody, Alexia Cardona, Elizabeth Selvin, Alicia K. Smith, Andrew H. Miller, Mylin A. Torres, Eirini Marouli, Xin Gào, Joyce B. J. Meurs, Johanna Graf-Schindler, Wolfgang Rathmann, Wolfgang Koenig, Annette Peters, Wolfgang Weninger, Matthias Farlik, Tao Zhang, Wei Chen, Yujing Xia, Alexander Teumer, Matthias Nauck, Hans J. Grabe, Macus Doerr, Terho Lehtimäki, Weihua Guan, Lili Milani, Toshiko Tanaka, Krista Fisher, Lindsay L. Waite, Silva Kasela, Paolo Vineis, Niek Verweij, Pim Harst, Licia Iacoviello, Carlotta Sacerdote, Salvatore Panico, Vittorio Krogh, Rosario Tumino, Evangelia Tzala, Giuseppe Matullo, Mikko A. Hurme, Olli T. Raitakari, Elena Colicino, Andrea A. Baccarelli, Mika Kähönen, Karl-Heinz Herzig, Shengxu Li, Karen N. Conneely, Jaspal S. Kooner, Anna Köttgen, Bastiaan T. Heijmans, Panos Deloukas, Caroline Relton, Ken K. Ong, Jordana T. Bell, Eric Boerwinkle, Paul Elliott, Hermann Brenner, Marian Beekman, Daniel Levy, Melanie Waldenberger, John C. Chambers, Abbas Dehghan and Marjo-Riitta Järvelin ()
Additional contact information
Matthias Wielscher: School of Public Health, Imperial College London
Pooja R. Mandaviya: Erasmus University Medical Center
Brigitte Kuehnel: Helmholtz Zentrum München, German Research Center for Environmental Health
Roby Joehanes: Framingham Heart Study
Rima Mustafa: School of Public Health, Imperial College London
Oliver Robinson: School of Public Health, Imperial College London
Yan Zhang: German Cancer Research Center
Barbara Bodinier: School of Public Health, Imperial College London
Esther Walton: University of Bath
Pashupati P. Mishra: Tampere University
Pascal Schlosser: Faculty of Medicine and Medical Center - University of Freiburg
Rory Wilson: Helmholtz Zentrum München, German Research Center for Environmental Health
Pei-Chien Tsai: King’s College London
Saranya Palaniswamy: School of Public Health, Imperial College London
Riccardo E. Marioni: University of Edinburgh
Giovanni Fiorito: University of Sassari
Giovanni Cugliari: Fondazione IRCCS Istituto Nazionale dei Tumori
Ville Karhunen: School of Public Health, Imperial College London
Mohsen Ghanbari: Erasmus MC University Medical Center
Bruce M. Psaty: University of Washington
Marie Loh: School of Public Health, Imperial College London
Joshua C. Bis: University of Washington
Benjamin Lehne: School of Public Health, Imperial College London
Nona Sotoodehnia: University of Washington
Ian J. Deary: University of Edinburgh
Marc Chadeau-Hyam: School of Public Health, Imperial College London
Jennifer A. Brody: University of Washington
Alexia Cardona: University of Cambridge
Elizabeth Selvin: Johns Hopkins Bloomberg School of Public Health
Alicia K. Smith: Emory University School of Medicine
Andrew H. Miller: Emory University School of Medicine
Mylin A. Torres: Winship Cancer Institute, Emory University School of Medicine
Eirini Marouli: Queen Mary University of London
Xin Gào: German Cancer Research Center
Joyce B. J. Meurs: Erasmus University Medical Center
Johanna Graf-Schindler: Helmholtz Zentrum München, German Research Center for Environmental Health
Wolfgang Rathmann: German Diabetes Center, Leibniz Center for Diabetes Resesarch at Heinrich Heine University Düsseldorf
Wolfgang Koenig: Technische Universität München
Annette Peters: Helmholtz Zentrum München, German Research Center for Environmental Health
Wolfgang Weninger: Medical University of Vienna
Matthias Farlik: Medical University of Vienna
Tao Zhang: Shandong University
Wei Chen: Tulane University
Yujing Xia: King’s College London
Alexander Teumer: University Medicine Greifswald
Matthias Nauck: Partner Site Greifswald
Hans J. Grabe: University Medicine Greifswald
Macus Doerr: Partner Site Greifswald
Terho Lehtimäki: Tampere University
Weihua Guan: University of Minnesota
Lili Milani: University of Tartu
Toshiko Tanaka: National Institute on Aging, National Institutes of Health
Krista Fisher: University of Tartu
Lindsay L. Waite: HudsonAlpha Institute for Biotechnology
Silva Kasela: University of Tartu
Paolo Vineis: School of Public Health, Imperial College London
Niek Verweij: University of Groningen, University Medical Center Groningen, Hanzeplein 1
Pim Harst: Division of Heart and Lungs, University Medical Center Utrecht
Licia Iacoviello: IRCCS NEUROMED
Carlotta Sacerdote: Citta’ della Salute e della Scienza Hospital and Centre for Cancer Prevention
Salvatore Panico: Dipartimento di Medicina Clinica e Chirurgia Federico II University
Vittorio Krogh: Fondazione IRCCS Istituto Nazionale dei Tumori
Rosario Tumino: “Civic - MPP Arezzo” Hospital, ASP Ragusa
Evangelia Tzala: School of Public Health, Imperial College London
Giuseppe Matullo: University of Turin
Mikko A. Hurme: Tampere University
Olli T. Raitakari: University of Turku
Elena Colicino: Icahn School of Medicine at Mount Sinai
Andrea A. Baccarelli: Columbia University Mailman School of Public Health
Mika Kähönen: Tampere University
Karl-Heinz Herzig: University of Oulu, and Oulu University Hospital
Shengxu Li: Children’s Minnesota
Karen N. Conneely: Emory University School of Medicine
Jaspal S. Kooner: National Heart and Lung Institute, Imperial College London
Anna Köttgen: Faculty of Medicine and Medical Center - University of Freiburg
Bastiaan T. Heijmans: Leiden University Medical Center
Panos Deloukas: Queen Mary University of London
Caroline Relton: Bristol Medical School, University of Bristol
Ken K. Ong: University of Cambridge
Jordana T. Bell: King’s College London
Eric Boerwinkle: University of Texas Health Science Center at Houston
Paul Elliott: School of Public Health, Imperial College London
Hermann Brenner: German Cancer Research Center
Marian Beekman: Leiden University Medical Center
Daniel Levy: Framingham Heart Study
Melanie Waldenberger: Helmholtz Zentrum München, German Research Center for Environmental Health
John C. Chambers: School of Public Health, Imperial College London
Abbas Dehghan: School of Public Health, Imperial College London
Marjo-Riitta Järvelin: School of Public Health, Imperial College London

Nature Communications, 2022, vol. 13, issue 1, 1-14

Abstract: Abstract We performed a multi-ethnic Epigenome Wide Association study on 22,774 individuals to describe the DNA methylation signature of chronic low-grade inflammation as measured by C-Reactive protein (CRP). We find 1,511 independent differentially methylated loci associated with CRP. These CpG sites show correlation structures across chromosomes, and are primarily situated in euchromatin, depleted in CpG islands. These genomic loci are predominantly situated in transcription factor binding sites and genomic enhancer regions. Mendelian randomization analysis suggests altered CpG methylation is a consequence of increased blood CRP levels. Mediation analysis reveals obesity and smoking as important underlying driving factors for changed CpG methylation. Finally, we find that an activated CpG signature significantly increases the risk for cardiometabolic diseases and COPD.

Date: 2022
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DOI: 10.1038/s41467-022-29792-6

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