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

Brenner H; Kasela S; Sotoodehnia N; Smith AK; Relton C; Doerr M; Wielscher M; Robinson O; Psaty BM; Baccarelli AA; Selvin E; Deloukas P; van Meurs JBJ; Marouli E; Mustafa R; Ghanbari M; Bell JT; Kahonen M; Krogh V; Teumer A; Levy D; Waldenberger M; Chambers JC; Brody JA; van der Harst P; Panico S; Colicino E; Hurme MA; Bis JC; Peters A; Guan WH; Karhunen V; Chen W; Kottgen A; Torres MA; Matullo G; Cardona A; Lehne B; Bodinier B; Nauck M; Tumino R; Fiorito G; Dehghan A; Verweij N; Schlosser P; Iacoviello L; Marioni RE; Kuehnel B; Graf-Schindler J; Kooner JS; Beekman M; Fisher K; Koenig W; Chadeau-Hyam M; Milani L; Tzala E; Vineis P; Waite LL; Lehtimaki T; Jarvelin MR; Conneely KN; Farlik M; Heijmans BT; Palaniswamy S; Deary IJ; Mandaviya PR; Rathmann W; Miller AH; Gao X; Herzig KH; Ong KK; Elliott P; Walton E; Cugliari G; Joehanes R; Zhang Y; Raitakari OT; Boerwinkle E; Wilson R; Loh M; Xia YJ; Grabe HJ; Tsai PC; Li SX; Mishra PP; Weninger W; Zhang T; Tanaka T; Sacerdote C

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

Brenner H
Kasela S
Sotoodehnia N
Smith AK
Relton C
Doerr M
Wielscher M
Robinson O
Psaty BM
Baccarelli AA
Selvin E
Deloukas P
van Meurs JBJ
Marouli E
Mustafa R
Ghanbari M
Bell JT
Kahonen M
Krogh V
Teumer A
Levy D
Waldenberger M
Chambers JC
Brody JA
van der Harst P
Panico S
Colicino E
Hurme MA
Bis JC
Peters A
Guan WH
Karhunen V
Chen W
Kottgen A
Torres MA
Matullo G
Cardona A
Lehne B
Bodinier B
Nauck M
Tumino R
Fiorito G
Dehghan A
Verweij N
Schlosser P
Iacoviello L
Marioni RE
Kuehnel B
Graf-Schindler J
Kooner JS
Beekman M
Fisher K
Koenig W
Chadeau-Hyam M
Milani L
Tzala E
Vineis P
Waite LL
Lehtimaki T
Jarvelin MR
Conneely KN
Farlik M
Heijmans BT
Palaniswamy S
Deary IJ
Mandaviya PR
Rathmann W
Miller AH
Gao X
Herzig KH
Ong KK
Elliott P
Walton E
Cugliari G
Joehanes R
Zhang Y
Raitakari OT
Boerwinkle E
Wilson R
Loh M
Xia YJ
Grabe HJ
Tsai PC
Li SX
Mishra PP
Weninger W
Zhang T
Tanaka T
Sacerdote C
Katso/Avaa
s41467-022-29792-6.pdf (2.228Mb)
Lataukset: 

NATURE PORTFOLIO
doi:10.1038/s41467-022-29792-6
URI
https://www.nature.com/articles/s41467-022-29792-6
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Julkaisun pysyvä osoite on:
https://urn.fi/URN:NBN:fi-fe2022081154854
Tiivistelmä
Chronic inflammation, marked by C-reactive protein, has been associated with changes in methylation, but the causal relationship is unclear. Here, the authors perform a Epigenome-wide association meta-analysis for C-reactive protein levels and find that these methylation changes are likely the consequence of inflammation and could contribute to disease.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.
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