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

BIOS Consortium; 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. 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; Terho Lehtimäki; Mikko A. Hurme; Mika Kähönen

doi:10.1038/s41467-022-29792-6

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

BIOS Consortium
, 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. 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, Terho Lehtimäki, Mikko A. Hurme, Mika Kähönen

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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
Number of pages	14
Journal	Nature Communications
Volume	13
DOIs	https://doi.org/10.1038/s41467-022-29792-6
Publication status	Published - 3 May 2022
Publication type	A1 Journal article-refereed

UN SDGs

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

SDG 3 Good Health and Well-being

Publication forum classification

Publication forum level 3

ASJC Scopus subject areas

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

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

s41467-022-29792-6Final published version, 2.25 MBLicence: CC BY

https://urn.fi/URN:NBN:fi:tuni-202206015405Licence: CC BY

Cite this

BIOS Consortium, Wielscher, M., Mandaviya, P. R., Kuehnel, B., Joehanes, R., Mustafa, R., Robinson, O., Zhang, Y., Bodinier, B., Walton, E., Mishra, P. P., Schlosser, P., Wilson, R., Tsai, P. C., Palaniswamy, S., Marioni, R. E., Fiorito, G., Cugliari, G., Karhunen, V., ... Kähönen, M. (2022). DNA methylation signature of chronic low-grade inflammation and its role in cardio-respiratory diseases. Nature Communications, 13, Article 2408. https://doi.org/10.1038/s41467-022-29792-6

@article{c85a1da0ec804bd99651c7422a15a3a7,

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 Yan Zhang and Barbara Bodinier and Esther Walton and Mishra, \{Pashupati P.\} and Pascal Schlosser and Rory Wilson and Tsai, \{Pei Chien\} 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 Xin G{\`a}o 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 Tao Zhang and Wei Chen and Yujing Xia and Alexander Teumer and Matthias Nauck and Grabe, \{Hans J.\} and Terho Lehtim{\"a}ki and Hurme, \{Mikko A.\} and Mika K{\"a}h{\"o}nen",

note = "Publisher Copyright: {\textcopyright} 2022. The Author(s).",

year = "2022",

month = may,

day = "3",

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

language = "English",

volume = "13",

journal = "Nature Communications",

issn = "2041-1723",

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BIOS Consortium, Wielscher, M, Mandaviya, PR, Kuehnel, B, Joehanes, R, Mustafa, R, Robinson, O, Zhang, Y, Bodinier, B, Walton, E, Mishra, PP, Schlosser, P, Wilson, R, Tsai, PC, Palaniswamy, S, Marioni, RE, Fiorito, G, Cugliari, G, Karhunen, V, Ghanbari, M, Psaty, BM, Loh, M, Bis, JC, Lehne, B, Sotoodehnia, N, Deary, IJ, Chadeau-Hyam, M, Brody, JA, Cardona, A, Selvin, E, Smith, AK, Miller, AH, Torres, MA, Marouli, E, Gào, X, van Meurs, JBJ, Graf-Schindler, J, Rathmann, W, Koenig, W, Peters, A, Weninger, W, Farlik, M, Zhang, T, Chen, W, Xia, Y, Teumer, A, Nauck, M, Grabe, HJ, Lehtimäki, T , Hurme, MA & Kähönen, M 2022, 'DNA methylation signature of chronic low-grade inflammation and its role in cardio-respiratory diseases', Nature Communications, vol. 13, 2408. https://doi.org/10.1038/s41467-022-29792-6

TY - JOUR

T1 - DNA methylation signature of chronic low-grade inflammation and its role in cardio-respiratory diseases

AU - BIOS Consortium

AU - Wielscher, Matthias

AU - Mandaviya, Pooja R.

AU - Kuehnel, Brigitte

AU - Joehanes, Roby

AU - Mustafa, Rima

AU - Robinson, Oliver

AU - Zhang, Yan

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 - Gào, Xin

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 - Zhang, Tao

AU - Chen, Wei

AU - Xia, Yujing

AU - Teumer, Alexander

AU - Nauck, Matthias

AU - Grabe, Hans J.

AU - Lehtimäki, Terho

AU - Hurme, Mikko A.

AU - Kähönen, Mika

PY - 2022/5/3

Y1 - 2022/5/3

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

AN - SCOPUS:85129996814

SN - 2041-1723

VL - 13

JO - Nature Communications

JF - Nature Communications

M1 - 2408

ER -

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

Abstract

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