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

BIOS consortium

doi:10.1038/s41467-022-29792-6

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

BIOS consortium

Research output: Contribution to journal › Article › peer-review

40 Citations (SciVal)

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 language	English
Article number	2408
Pages (from-to)	2408
Journal	Nature Communications
Volume	13
Issue number	1
DOIs	https://doi.org/10.1038/s41467-022-29792-6
Publication status	Published - 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).

ASJC Scopus subject areas

General Chemistry
General Biochemistry,Genetics and Molecular Biology
General
General Physics and Astronomy

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41467-022-29792-6Licence: CC BY

Cite this

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

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.",

author = "{BIOS consortium} and Matthias Wielscher and Mandaviya, {Pooja R} and Brigitte Kuehnel and Roby Joehanes and Rima Mustafa and Oliver Robinson and Barbara Bodinier and Esther Walton and Mishra, {Pashupati P} and Pascal Schlosser and Rory Wilson and Pei-Chien Tsai and Saranya Palaniswamy and Marioni, {Riccardo E} and Giovanni Fiorito and Giovanni Cugliari and Ville Karhunen and Mohsen Ghanbari and Psaty, {Bruce M} and Marie Loh and Bis, {Joshua C} and Benjamin Lehne and Nona Sotoodehnia and Deary, {Ian J} and Marc Chadeau-Hyam and Brody, {Jennifer A} and Alexia Cardona and Elizabeth Selvin and Smith, {Alicia K} and Miller, {Andrew H} and Torres, {Mylin A} and Eirini Marouli and {van Meurs}, {Joyce B J} and Johanna Graf-Schindler and Wolfgang Rathmann and Wolfgang Koenig and Annette Peters and Wolfgang Weninger and Matthias Farlik and Wei Chen and Yujing Xia and Alexander Teumer and Matthias Nauck and Grabe, {Hans J} and Macus Doerr and Terho Lehtim{\"a}ki and Weihua Guan and Lili Milani and Toshiko Tanaka and Krista Fisher",

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: {\textcopyright} 2022, The Author(s).",

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doi = "10.1038/s41467-022-29792-6",

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AU - Wielscher, Matthias

AU - Mandaviya, Pooja R

AU - Kuehnel, Brigitte

AU - Joehanes, Roby

AU - Mustafa, Rima

AU - Robinson, Oliver

AU - Bodinier, Barbara

AU - Walton, Esther

AU - Mishra, Pashupati P

AU - Schlosser, Pascal

AU - Wilson, Rory

AU - Tsai, Pei-Chien

AU - Palaniswamy, Saranya

AU - Marioni, Riccardo E

AU - Fiorito, Giovanni

AU - Cugliari, Giovanni

AU - Karhunen, Ville

AU - Ghanbari, Mohsen

AU - Psaty, Bruce M

AU - Loh, Marie

AU - Bis, Joshua C

AU - Lehne, Benjamin

AU - Sotoodehnia, Nona

AU - Deary, Ian J

AU - Chadeau-Hyam, Marc

AU - Brody, Jennifer A

AU - Cardona, Alexia

AU - Selvin, Elizabeth

AU - Smith, Alicia K

AU - Miller, Andrew H

AU - Torres, Mylin A

AU - Marouli, Eirini

AU - van Meurs, Joyce B J

AU - Graf-Schindler, Johanna

AU - Rathmann, Wolfgang

AU - Koenig, Wolfgang

AU - Peters, Annette

AU - Weninger, Wolfgang

AU - Farlik, Matthias

AU - Chen, Wei

AU - Xia, Yujing

AU - Teumer, Alexander

AU - Nauck, Matthias

AU - Grabe, Hans J

AU - Doerr, Macus

AU - Lehtimäki, Terho

AU - Guan, Weihua

AU - Milani, Lili

AU - Tanaka, Toshiko

AU - Fisher, Krista

N1 - 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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N2 - 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.

AB - 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.

U2 - 10.1038/s41467-022-29792-6

DO - 10.1038/s41467-022-29792-6

M3 - Article

C2 - 35504910

SN - 2041-1723

VL - 13

SP - 2408

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 2408

ER -

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

Abstract

Bibliographical note

ASJC Scopus subject areas

UN SDGs

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