DNA methylation signature of chronic low-grade inflammation and its role in cardio-respiratory diseases.
Authors
Mandaviya, Pooja R
Kuehnel, Brigitte
Joehanes, Roby
Zhang, Yan
Mishra, Pashupati P
Tsai, Pei-Chien
Marioni, Riccardo E
Fiorito, Giovanni
Cugliari, Giovanni
Lehne, Benjamin
Sotoodehnia, Nona
Deary, Ian J
Selvin, Elizabeth
Torres, Mylin A
van Meurs, Joyce BJ
Graf-Schindler, Johanna
Rathmann, Wolfgang
Weninger, Wolfgang
Zhang, Tao
Grabe, Hans J
Guan, Weihua
Tanaka, Toshiko
Waite, Lindsay L
Kasela, Silva
Vineis, Paolo
Verweij, Niek
Iacoviello, Licia
Sacerdote, Carlotta
Panico, Salvatore
Tumino, Rosario
Tzala, Evangelia
Matullo, Giuseppe
Hurme, Mikko A
Raitakari, Olli T
Colicino, Elena
Baccarelli, Andrea A
Kähönen, Mika
BIOS consortium
Conneely, Karen N
Kooner, Jaspal S
Relton, Caroline
Boerwinkle, Eric
Levy, Daniel
Publication Date
2022-05-03Journal Title
Nat Commun
ISSN
2041-1723
Publisher
Springer Science and Business Media LLC
Volume
13
Issue
1
Language
en
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Wielscher, M., Mandaviya, P. R., Kuehnel, B., Joehanes, R., Mustafa, R., Robinson, O., Zhang, Y., et al. (2022). DNA methylation signature of chronic low-grade inflammation and its role in cardio-respiratory diseases.. Nat Commun, 13 (1) https://doi.org/10.1038/s41467-022-29792-6
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.
Keywords
Article, /631/208/176/1988, /692/163/2743/393, /692/499, /45/61, /38, article
Sponsorship
MRC (MC_UU_00006/2)
Identifiers
s41467-022-29792-6, 29792
External DOI: https://doi.org/10.1038/s41467-022-29792-6
This record's URL: https://www.repository.cam.ac.uk/handle/1810/336827
Rights
Licence:
http://creativecommons.org/licenses/by/4.0/
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