The EPIC-Norfolk Study
DNA methylation signature of chronic low-grade inflammation and its role in cardio-respiratory diseases.
Nature communications 2021 ; 13: 2408.
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, Doerr M, Lehtimäki T, Guan W, Milani L, Tanaka T, Fisher K, Waite LL, Kasela S, Vineis P, Verweij N, van der Harst P, Iacoviello L, Sacerdote C, Panico S, Krogh V, Tumino R, Tzala E, Matullo G, Hurme MA, Raitakari OT, Colicino E, Baccarelli AA, Kähönen M, Herzig KH, Li S, BIOS consortium BIOS consortium, Conneely KN, Kooner JS, Köttgen A, Heijmans BT, Deloukas P, Relton C, Ong KK, Bell JT, Boerwinkle E, Elliott P, Brenner H, Beekman M, Levy D, Waldenberger M, Chambers JC, Dehghan A, and Järvelin MR
DOI : 10.1038/s41467-022-29792-6
PubMed ID : 35504910
PMCID : PMC9065016
URL : https://www.nature.com/articles/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.