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

Research output: Contribution to journalArticlepeer-review

BIOS Consortium

Original languageEnglish
Pages (from-to)2408
Number of pages1
JournalNature Communications
Volume13
Issue number1
DOIs
Published3 May 2022

Bibliographical note

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

King's Authors

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.

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