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.

• Authors: 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, Macus Doerr, Terho Lehtimäki, Weihua Guan, Lili Milani, Toshiko Tanaka, Krista Fisher, Lindsay L Waite, Silva Kasela, Paolo Vineis, Niek Verweij, Pim van der Harst, Licia Iacoviello, Carlotta Sacerdote, Salvatore Panico, Vittorio Krogh, Rosario Tumino, Evangelia Tzala, Giuseppe Matullo, Mikko A Hurme, Olli T Raitakari, Elena Colicino, Andrea A Baccarelli, Mika Kähönen, Karl-Heinz Herzig, Shengxu Li, BIOS consortium, Karen N Conneely, Jaspal S Kooner, Anna Köttgen, Bastiaan T Heijmans, Panos Deloukas, Caroline Relton, Ken K Ong, Jordana T Bell, Eric Boerwinkle, Paul Elliott, Hermann Brenner, Marian Beekman, Daniel Levy, Melanie Waldenberger, John C Chambers, Abbas Dehghan, Marjo-Riitta Järvelin
• Journal: Nature communications (Nat Commun) Vol. 13 Issue 1 Pg. 2408 (05 03 2022) ISSN: 2041-1723 [Electronic] England
• PMID: 35504910 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural)
• Copyright: © 2022. The Author(s).

Chemical References

• C-Reactive Protein

Topics

• C-Reactive Protein (genetics)
• CpG Islands (genetics)
• DNA Methylation (genetics)
• Humans
• Inflammation (genetics)
• Nucleotide Motifs