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

Matthias Wielscher*, Pooja R. Mandaviya, BIOS Consortium, 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 GhanbariBruce 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. van 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, Niek Verweij, Jordana T. Bell, Abbas Dehghan

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Scopus)

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.

Original languageEnglish
Article number2408
JournalNature Communications
Volume13
Issue number1
DOIs
Publication statusPublished - 3 May 2022

Bibliographical note

Funding Information:
H.J.G. has received travel grants and speakers honoraria from Fresenius Medical Care, Neuraxpharm, Servier, and Janssen Cilag as well as research funding from Fresenius Medical Care. All other study authors declare no competing interests.

Publisher Copyright:
© 2022, The Author(s).

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