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

TitleDNA methylation signature of chronic low-grade inflammation and its role in cardio-respiratory diseases.
Publication TypeJournal Article
Year of Publication2022
AuthorsWielscher M, Mandaviya PR, Kuehnel B, Joehanes R, Mustafa R, Robinson O, Zhang Y, Bodinier B, Walton E, Mishra PP, Schlosser P, Wilson R, Tsai P-C, 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, Gao 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 K-H, Li S, 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, Jarvelin M-R
Corporate AuthorsBIOS Consortium
JournalNat Commun
Volume13
Issue1
Pagination2408
Date Published2022 05 03
ISSN2041-1723
KeywordsC-Reactive Protein, CpG Islands, DNA Methylation, Humans, Inflammation, Nucleotide Motifs
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.

DOI10.1038/s41467-022-29792-6
Alternate JournalNat Commun
PubMed ID35504910
PubMed Central IDPMC9065016
Grant ListK24 HL152440 / HL / NHLBI NIH HHS / United States
MR/S03532X/1 / MRC_ / Medical Research Council / United Kingdom
MR/R023484/1 / MRC_ / Medical Research Council / United Kingdom
16/136/68 / DH_ / Department of Health / United Kingdom
MR/L01632X/1 / MRC_ / Medical Research Council / United Kingdom
MR/S019669/1 / MRC_ / Medical Research Council / United Kingdom
RE/18/4/34215 / BHF_ / British Heart Foundation / United Kingdom
217065/Z/19/Z / WT_ / Wellcome Trust / United Kingdom
WT092830/Z/10/Z / WT_ / Wellcome Trust / United Kingdom
BBI025751/1 / BB_ / Biotechnology and Biological Sciences Research Council / United Kingdom
BB/I025263/1 / BB_ / Biotechnology and Biological Sciences Research Council / United Kingdom
MC_UU_00011/5 / MRC_ / Medical Research Council / United Kingdom
G1001357 / MRC_ / Medical Research Council / United Kingdom
HHSN268201700001I / HL / NHLBI NIH HHS / United States
HHSN268201700002I / HL / NHLBI NIH HHS / United States
HHSN268201700003I / HL / NHLBI NIH HHS / United States
HHSN268201700004I / HL / NHLBI NIH HHS / United States
HHSN268201700005I / HL / NHLBI NIH HHS / United States
R01 HL087641 / HL / NHLBI NIH HHS / United States
R01 HL059367 / HL / NHLBI NIH HHS / United States
R01 HL086694 / HL / NHLBI NIH HHS / United States
U01 HG004402 / HG / NHGRI NIH HHS / United States
RC2 HL102419 / HL / NHLBI NIH HHS / United States
R01 NS087541 / NS / NINDS NIH HHS / United States
R01 HL131136 / HL / NHLBI NIH HHS / United States
UL1 RR025005 / RR / NCRR NIH HHS / United States
R01 HL105756 / HL / NHLBI NIH HHS / United States
HHSN268201200036C / HL / NHLBI NIH HHS / United States
HHSN268200800007C / HL / NHLBI NIH HHS / United States
HHSN268201800001C / HL / NHLBI NIH HHS / United States
N01HC55222 / HL / NHLBI NIH HHS / United States
N01HC85079 / HL / NHLBI NIH HHS / United States
N01HC85080 / HL / NHLBI NIH HHS / United States
N01HC85081 / HL / NHLBI NIH HHS / United States
N01HC85082 / HL / NHLBI NIH HHS / United States
N01HC85083 / HL / NHLBI NIH HHS / United States
N01HC85086 / HL / NHLBI NIH HHS / United States
R01 AG023629 / AG / NIA NIH HHS / United States
75N92021D00006 / HL / NHLBI NIH HHS / United States
U01 HL080295 / HL / NHLBI NIH HHS / United States
U01 HL130114 / HL / NHLBI NIH HHS / United States
K08 HL116640 / HL / NHLBI NIH HHS / United States
R01 HL087652 / HL / NHLBI NIH HHS / United States
R01 HL092111 / HL / NHLBI NIH HHS / United States
R01 HL103612 / HL / NHLBI NIH HHS / United States
R01 HL105756 / HL / NHLBI NIH HHS / United States
R01 HL103612 / HL / NHLBI NIH HHS / United States
R01 HL111089 / HL / NHLBI NIH HHS / United States
R01 HL116747 / HL / NHLBI NIH HHS / United States
R01 HL120393 / HL / NHLBI NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
MR/M01311/1 / MRC_ / Medical Research Council / United Kingdom
212945/Z/18/Z / WT_ / Wellcome Trust / United Kingdom
G0601653 / MRC_ / Medical Research Council / United Kingdom
WT081878MA / WT_ / Wellcome Trust / United Kingdom
WT202786/Z/16/Z / WT_ / Wellcome Trust / United Kingdom
BB/S020845/1 / BB_ / Biotechnology and Biological Sciences Research Council / United Kingdom
BB/T019980/1 / BB_ / Biotechnology and Biological Sciences Research Council / United Kingdom