DNA methylation signature of chronic low-grade inflammation and its role in cardio-respiratory diseases-Reference-Cited by-同舟云学术

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

Published:2022-05-03 Issue:1 Volume:13 Page:
ISSN:2041-1723
Container-title:Nature Communications
language:en
Short-container-title:Nat Commun

Author:

Wielscher Matthias^ORCID,Mandaviya Pooja R.,Kuehnel Brigitte,Joehanes Roby,Mustafa Rima^ORCID,Robinson Oliver^ORCID,Zhang Yan,Bodinier Barbara^ORCID,Walton Esther^ORCID,Mishra Pashupati P.,Schlosser Pascal^ORCID,Wilson Rory^ORCID,Tsai Pei-Chien,Palaniswamy Saranya^ORCID,Marioni Riccardo E.,Fiorito Giovanni,Cugliari Giovanni,Karhunen Ville^ORCID,Ghanbari Mohsen^ORCID,Psaty Bruce M.^ORCID,Loh Marie^ORCID,Bis Joshua C.^ORCID,Lehne Benjamin,Sotoodehnia Nona,Deary Ian J.,Chadeau-Hyam Marc^ORCID,Brody Jennifer A.^ORCID,Cardona Alexia^ORCID,Selvin Elizabeth,Smith Alicia K.^ORCID,Miller Andrew H.^ORCID,Torres Mylin A.,Marouli Eirini^ORCID,Gào Xin^ORCID,van Meurs Joyce B. J.,Graf-Schindler Johanna,Rathmann Wolfgang,Koenig Wolfgang^ORCID,Peters Annette^ORCID,Weninger Wolfgang,Farlik Matthias^ORCID,Zhang Tao,Chen Wei^ORCID,Xia Yujing^ORCID,Teumer Alexander^ORCID,Nauck Matthias^ORCID,Grabe Hans J.,Doerr Macus^ORCID,Lehtimäki Terho^ORCID,Guan Weihua,Milani Lili^ORCID,Tanaka Toshiko,Fisher Krista^ORCID,Waite Lindsay L.,Kasela Silva,Vineis Paolo,Verweij Niek,van der Harst Pim^ORCID,Iacoviello Licia,Sacerdote Carlotta,Panico Salvatore,Krogh Vittorio^ORCID,Tumino Rosario,Tzala Evangelia,Matullo Giuseppe,Hurme Mikko A.,Raitakari Olli T.,Colicino Elena,Baccarelli Andrea A.,Kähönen Mika,Herzig Karl-Heinz^ORCID,Li Shengxu^ORCID,Conneely Karen N.,Kooner Jaspal S.,Köttgen Anna^ORCID,Heijmans Bastiaan T.^ORCID,Deloukas Panos^ORCID,Relton Caroline,Ong Ken K.^ORCID,Bell Jordana T.^ORCID,Boerwinkle Eric,Elliott Paul^ORCID,Brenner Hermann^ORCID,Beekman Marian^ORCID,Levy Daniel,Waldenberger Melanie^ORCID,Chambers John C.^ORCID,Dehghan Abbas^ORCID,Järvelin Marjo-Riitta^ORCID,

Abstract

AbstractWe 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.

Funder

EC | Horizon 2020 Framework Programme

Publisher

Springer Science and Business Media LLC

Subject

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

Link

https://www.nature.com/articles/s41467-022-29792-6.pdf

Reference65 articles.

1. Danesh, J. et al. Low grade inflammation and coronary heart disease: prospective study and updated meta-analyses. BMJ 321, 199–204 (2000).

2. Dehghan, A. et al. Risk of type 2 diabetes attributable to C-reactive protein and other risk factors. Diabetes Care 30, 2695–9 (2007).

3. Schmidt, M. I. et al. Markers of inflammation and prediction of diabetes mellitus in adults (Atherosclerosis Risk in Communities study): A cohort study. Lancet 353, 1649–52 (1999).