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Get Free Access<title>Abstract</title> We performed a trans-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 found 1,511 independent differentially methylated loci associated with CRP. These CpG sites showed correlation structures across chromosomes, and were primarily situated in euchromatin, depleted in CpG islands and enriched in transcription factor binding sites and genomic enhancer regions. Mendelian randomisation analysis suggests altered CpG methylation is a consequence of increased blood CRP levels. Mediation analysis revealed obesity and smoking as important underlying driving factors for changed CpG methylation. Finally, we found that a fully activated CpG signature, meaning that if all novel discovered CpGs would either be fully methylated or unmethylated depending on their CRP associated direction of effect, the risk of myocardial infarction would be increased by 20.3%, risk of T2D by 11.3% and the risk of COPD by 5.6%.
Matthias Wielscher, Pooja R. Mandaviya, Brigitte Kuehnel, Roby Joehanes, Rima Mustafa, Oliver Robinson, Tao 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 Torres, Eirini Marouli, Xīn Gào, Joyce B. J. van Meurs, Johanna Graf-Schindler, Wolfgang Rathmann, Wolfgang Köenig, Annette Peters, Wolfgang Weninger, Matthias Farlik, Yan Zhang, Wei Chen, Yujing Xia, Alexander Teumer, Matthias Nauck, Hans J. Grabe, Marcus Dörr, Terho Lehtimäki, Weihua Guan, Lili Milani, Toshiko Tanaka, Krista Fischer, 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 Hurme, Olli Raitakari, Elena Colicino, Andrea Baccarelli, Mika Kähönen, Karl‐Heinz Herzig, Shengxu Li, Bastiaan T. Heijmans, Karen N. Conneely, Jaspal S. Kooner, Anna Köttgen, Panos Deloukas, Caroline L. Relton, Ken K. Ong, Jordana T. Bell, Eric Boerwinkle, Paul Elliott, Hermann Brenner, Marian Beekman, Daniel Levy, Mélanie Waldenberger, John C. Chambers, Abbas Dehghan, Paul M Ridker (2021). DNA methylation signature of chronic low-grade inflammation and its role in cardio-respiratory diseases. , DOI: https://doi.org/10.21203/rs.3.rs-688986/v1.
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Type
Preprint
Year
2021
Authors
89
Datasets
0
Total Files
0
Language
en
DOI
https://doi.org/10.21203/rs.3.rs-688986/v1
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