DNA methylation signature of chronic low-grade inflammation and its role in cardio-respiratory diseases.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
03 05 2022
03 05 2022
Historique:
received:
05
07
2021
accepted:
31
03
2022
entrez:
3
5
2022
pubmed:
4
5
2022
medline:
6
5
2022
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 35504910
doi: 10.1038/s41467-022-29792-6
pii: 10.1038/s41467-022-29792-6
pmc: PMC9065016
doi:
Substances chimiques
C-Reactive Protein
9007-41-4
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
2408Subventions
Organisme : NHLBI NIH HHS
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Pays : United States
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Organisme : NHLBI NIH HHS
ID : HHSN268201800001C
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ID : U01 HL080295
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ID : R01 HL120393
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Organisme : NHLBI NIH HHS
ID : HHSN268201200036C
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ID : RC2 HL102419
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ID : R01 NS087541
Pays : United States
Organisme : Wellcome Trust
ID : WT081878MA
Pays : United Kingdom
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ID : R01 HL103612
Pays : United States
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Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201700001I
Pays : United States
Organisme : Medical Research Council
ID : MC_UU_00006/2
Pays : United Kingdom
Organisme : Wellcome Trust
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Organisme : NHLBI NIH HHS
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Organisme : Wellcome Trust
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Pays : United States
Organisme : Wellcome Trust
ID : 212945/Z/18/Z
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Pays : United States
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Organisme : Biotechnology and Biological Sciences Research Council
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Organisme : NHLBI NIH HHS
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Organisme : British Heart Foundation
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Pays : United Kingdom
Organisme : NHLBI NIH HHS
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Organisme : Wellcome Trust
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Organisme : NHLBI NIH HHS
ID : R01 HL087641
Pays : United States
Organisme : British Heart Foundation
ID : RE/18/4/34215
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Organisme : NHLBI NIH HHS
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Organisme : NHLBI NIH HHS
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Organisme : Medical Research Council
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Organisme : NHLBI NIH HHS
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Pays : United States
Organisme : Medical Research Council
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Organisme : NHLBI NIH HHS
ID : N01HC85081
Pays : United States
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/T019980/1
Pays : United Kingdom
Informations de copyright
© 2022. The Author(s).
Références
PLoS Med. 2016 Jun 21;13(6):e1001976
pubmed: 27327646
BMC Bioinformatics. 2012 May 08;13:86
pubmed: 22568884
Cell. 2014 Jan 16;156(1-2):45-68
pubmed: 24439369
Eur J Hum Genet. 2011 Jul;19(7):807-12
pubmed: 21407268
J Hum Hypertens. 2003 Apr;17(4):223-30
pubmed: 12692566
Sci Adv. 2018 Jan 31;4(1):eaao4364
pubmed: 29399631
Nat Commun. 2019 Sep 19;10(1):4267
pubmed: 31537805
Bioinformatics. 2014 May 15;30(10):1363-9
pubmed: 24478339
Lancet. 1999 May 15;353(9165):1649-52
pubmed: 10335783
BMJ. 2018 Jul 12;362:k601
pubmed: 30002074
Am J Hum Genet. 2006 Feb;78(2):350-6
pubmed: 16400614
Eur Respir J. 2013 Oct;42(4):964-71
pubmed: 23429915
J Allergy Clin Immunol. 2019 Jun;143(6):2062-2074
pubmed: 30579849
Cell. 2014 Dec 18;159(7):1665-80
pubmed: 25497547
Clin Epigenetics. 2019 Jul 1;11(1):97
pubmed: 31262328
Nat Commun. 2020 Apr 20;11(1):1898
pubmed: 32313055
Diabetes Care. 2007 Oct;30(10):2695-9
pubmed: 17623828
Circulation. 2003 Feb 11;107(5):671-4
pubmed: 12578865
Gastroenterology. 2019 Jun;156(8):2254-2265.e3
pubmed: 30779925
Int J Epidemiol. 2016 Dec 1;45(6):1866-1886
pubmed: 28108528
Circ Cardiovasc Genet. 2016 Oct;9(5):436-447
pubmed: 27651444
J Affect Disord. 2013 Sep 25;150(3):736-44
pubmed: 23870425
Mol Cell. 2016 May 5;62(3):422-431
pubmed: 27153539
N Engl J Med. 2004 Apr 1;350(14):1387-97
pubmed: 15070788
Nat Clin Pract Oncol. 2005 Dec;2 Suppl 1:S4-11
pubmed: 16341240
N Engl J Med. 2018 Dec 20;379(25):2429-2437
pubmed: 30575491
Cell Metab. 2011 Jan 5;13(1):11-22
pubmed: 21195345
Nature. 2017 Jan 5;541(7635):81-86
pubmed: 28002404
Genome Biol. 2017 Jan 27;18(1):19
pubmed: 28129774
Genome Biol. 2016 Oct 7;17(1):208
pubmed: 27717381
Nat Med. 2019 Dec;25(12):1822-1832
pubmed: 31806905
Am J Hum Genet. 2018 Nov 1;103(5):691-706
pubmed: 30388399
Nat Commun. 2020 Jan 3;11(1):15
pubmed: 31900413
Nature. 2015 Feb 19;518(7539):317-30
pubmed: 25693563
Front Immunol. 2018 Apr 13;9:754
pubmed: 29706967
Sci Rep. 2018 Aug 24;8(1):12816
pubmed: 30143687
Genome Biol. 2016 Dec 12;17(1):255
pubmed: 27955697
Lancet Diabetes Endocrinol. 2014 Nov;2(11):867-74
pubmed: 25128274
Cell. 2014 Mar 27;157(1):95-109
pubmed: 24679529
Eur Respir Rev. 2017 Jan 31;26(143):
pubmed: 28143876
Eur Respir J. 2019 Jul 4;54(1):
pubmed: 31073081
Clin Exp Immunol. 2007 Feb;147(2):227-35
pubmed: 17223962
Sci Rep. 2019 Mar 5;9(1):3450
pubmed: 30837600
Int J Obes (Lond). 2011 Feb;35(2):300-8
pubmed: 20714329
Mol Cell Biol. 2007 Apr;27(7):2746-57
pubmed: 17242185
Front Hum Neurosci. 2017 Jun 20;11:316
pubmed: 28676747
BMJ. 2000 Jul 22;321(7255):199-204
pubmed: 10903648
Nucleic Acids Res. 1994 Jun 25;22(12):2417-22
pubmed: 8036173
Nat Commun. 2017 Mar 17;8:14617
pubmed: 28303888
J Allergy Clin Immunol. 2020 Oct;146(4):694-705
pubmed: 32771559
Eur J Nutr. 2014 Feb;53(1):39-48
pubmed: 23389112
J Am Coll Cardiol. 2005 May 17;45(10):1563-9
pubmed: 15893167
J Clin Endocrinol Metab. 2010 Jan;95(1):93-9
pubmed: 19906786
Nature. 2012 Apr 11;485(7398):376-80
pubmed: 22495300
Nat Commun. 2018 Jun 19;9(1):2397
pubmed: 29921915
Genome Med. 2021 Jun 21;13(1):104
pubmed: 34154662
Lancet Diabetes Endocrinol. 2015 Jul;3(7):526-534
pubmed: 26095709
Nucleic Acids Res. 2013 Jan;41(Database issue):D171-6
pubmed: 23203885
Nucleic Acids Res. 2019 Jan 8;47(D1):D983-D988
pubmed: 30364969
Genome Biol. 2014 Apr 01;15(4):r54
pubmed: 24690455
JAMA Cardiol. 2019 May 1;4(5):455-459
pubmed: 30916719
Clin Epigenetics. 2021 Mar 22;13(1):60
pubmed: 33752734
Epigenetics. 2013 Feb;8(2):203-9
pubmed: 23314698
Lancet Respir Med. 2018 May;6(5):379-388
pubmed: 29496485
Lancet. 1999 Jan 9;353(9147):89-92
pubmed: 10023892