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

Published version
Peer-reviewed

Type

Article

Change log

Authors

Wielscher, Matthias  ORCID logo  https://orcid.org/0000-0003-4138-1383
Mandaviya, Pooja R 
Kuehnel, Brigitte 
Joehanes, Roby 

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.

Description

Keywords

C-Reactive Protein, CpG Islands, DNA Methylation, Humans, Inflammation, Nucleotide Motifs

Journal Title

Nat Commun

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

13

Publisher

Springer Science and Business Media LLC
Sponsorship
MRC (MC_UU_00006/2)