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

Matthias Wielscher | Pooja R Mandaviya | Brigitte Kuehnel | Roby Joehanes | Rima Mustafa | Oliver Robinson | Yan 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 A Torres | Eirini Marouli | Xin Gào | Joyce B J van Meurs | Johanna Graf-Schindler | Wolfgang Rathmann | Wolfgang Koenig | Annette Peters | Wolfgang Weninger | Matthias Farlik | Tao Zhang | Wei Chen | Yujing Xia | Alexander Teumer | Matthias Nauck | Hans J Grabe | Macus Doerr | Terho Lehtimäki | Weihua Guan | Lili Milani | Toshiko Tanaka | Krista Fisher | 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 A Hurme | Olli T Raitakari | Elena Colicino | Andrea A Baccarelli | Mika Kähönen | Karl-Heinz Herzig | Shengxu Li | BIOS consortium | Karen N Conneely | Jaspal S Kooner | Anna Köttgen | Bastiaan T Heijmans | Panos Deloukas | Caroline Relton | Ken K Ong | Jordana T Bell | Eric Boerwinkle | Paul Elliott | Hermann Brenner | Marian Beekman | Daniel Levy | Melanie Waldenberger | John C Chambers | Abbas Dehghan | Marjo-Riitta Järvelin
Nature communications | 2022

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.

Pubmed ID: 35504910

Research resources used in this publication

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Associated grants

  • Agency: NHLBI NIH HHS, United States
    Id: 75N92021D00006
  • Agency: NHLBI NIH HHS, United States
    Id: N01HC85082
  • Agency: NHLBI NIH HHS, United States
    Id: HHSN268201700002I
  • Agency: NHLBI NIH HHS, United States
    Id: HHSN268200800007C
  • Agency: Biotechnology and Biological Sciences Research Council, United Kingdom
    Id: BB/I025263/1
  • Agency: Medical Research Council, United Kingdom
    Id: MC_UU_00011/5
  • Agency: Medical Research Council, United Kingdom
    Id: MR/K026992/1
  • Agency: Medical Research Council, United Kingdom
    Id: G1001357
  • Agency: NHLBI NIH HHS, United States
    Id: N01HC85080
  • Agency: NCATS NIH HHS, United States
    Id: UL1 TR000124
  • Agency: Biotechnology and Biological Sciences Research Council, United Kingdom
    Id: BB/S020845/1
  • Agency: NHLBI NIH HHS, United States
    Id: R01 HL086694
  • Agency: Department of Health, United Kingdom
    Id: 16/136/68
  • Agency: NHLBI NIH HHS, United States
    Id: R01 HL131136
  • Agency: Medical Research Council, United Kingdom
    Id: MR/R023484/1
  • Agency: NIA NIH HHS, United States
    Id: R01 AG023629
  • Agency: NHLBI NIH HHS, United States
    Id: HHSN268201800001C
  • Agency: NHLBI NIH HHS, United States
    Id: U01 HL080295
  • Agency: NHLBI NIH HHS, United States
    Id: R01 HL120393
  • Agency: NHLBI NIH HHS, United States
    Id: HHSN268201200036C
  • Agency: NHLBI NIH HHS, United States
    Id: RC2 HL102419
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS087541
  • Agency: Wellcome Trust, United Kingdom
    Id: WT081878MA
  • Agency: NHLBI NIH HHS, United States
    Id: R01 HL103612
  • Agency: NHLBI NIH HHS, United States
    Id: K08 HL116640
  • Agency: NHLBI NIH HHS, United States
    Id: HHSN268201700001I
  • Agency: Medical Research Council, United Kingdom
    Id: MC_UU_00006/2
  • Agency: Wellcome Trust, United Kingdom
    Id: WT202786/Z/16/Z
  • Agency: NHLBI NIH HHS, United States
    Id: R01 HL092111
  • Agency: Wellcome Trust, United Kingdom
    Id: 217065/Z/19/Z
  • Agency: Medical Research Council, United Kingdom
    Id: MR/S03532X/1
  • Agency: NHLBI NIH HHS, United States
    Id: HHSN268201700004I
  • Agency: NHLBI NIH HHS, United States
    Id: R01 HL105756
  • Agency: NCRR NIH HHS, United States
    Id: UL1 RR025005
  • Agency: Wellcome Trust, United Kingdom
    Id: 212945/Z/18/Z
  • Agency: NHLBI NIH HHS, United States
    Id: N01HC55222
  • Agency: NHLBI NIH HHS, United States
    Id: R01 HL111089
  • Agency: Biotechnology and Biological Sciences Research Council, United Kingdom
    Id: BBI025751/1
  • Agency: NHLBI NIH HHS, United States
    Id: N01HC85079
  • Agency: NHLBI NIH HHS, United States
    Id: R01 HL059367
  • Agency: Medical Research Council, United Kingdom
    Id: MR/M01311/1
  • Agency: NHLBI NIH HHS, United States
    Id: N01HC85083
  • Agency: NHGRI NIH HHS, United States
    Id: U01 HG004402
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    Id: N01HC85086
  • Agency: Medical Research Council, United Kingdom
    Id: MR/S019669/1
  • Agency: NHLBI NIH HHS, United States
    Id: HHSN268201700005I
  • Agency: British Heart Foundation, United Kingdom
    Id: RG/14/5/30893
  • Agency: NHLBI NIH HHS, United States
    Id: HHSN268201700003I
  • Agency: Wellcome Trust, United Kingdom
    Id: WT092830/Z/10/Z
  • Agency: NHLBI NIH HHS, United States
    Id: R01 HL087641
  • Agency: British Heart Foundation, United Kingdom
    Id: RE/18/4/34215
  • Agency: NHLBI NIH HHS, United States
    Id: U01 HL130114
  • Agency: NHLBI NIH HHS, United States
    Id: R01 HL087652
  • Agency: Medical Research Council, United Kingdom
    Id: G0601653
  • Agency: NHLBI NIH HHS, United States
    Id: R01 HL116747
  • Agency: Medical Research Council, United Kingdom
    Id: MR/L01632X/1
  • Agency: NHLBI NIH HHS, United States
    Id: N01HC85081
  • Agency: Biotechnology and Biological Sciences Research Council, United Kingdom
    Id: BB/T019980/1

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This is a list of tools and resources that we have found mentioned in this publication.


PLINK (tool)

RRID:SCR_001757

Open source whole genome association analysis toolset, designed to perform range of basic, large scale analyses in computationally efficient manner. Used for analysis of genotype/phenotype data. Through integration with gPLINK and Haploview, there is some support for subsequent visualization, annotation and storage of results. PLINK 1.9 is improved and second generation of the software.

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METAL (tool)

RRID:SCR_002013

Software application designed to facilitate meta-analysis of large datasets (such as several whole genome scans) in a convenient, rapid and memory efficient manner. (entry from Genetic Analysis Software)

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Binding and Expression Target Analysis (tool)

RRID:SCR_005396

A software package that integrates ChIP-seq of transcription factors or chromatin regulators with differential gene expression data to infer direct target genes. BETA has three functions: (1) to predict whether the factor has activating or repressive function; (2) to infer the factor''''s target genes; and (3) to identify the motif of the factor and its collaborators which might modulate the factor''''s activating or repressive function. BETA requires ~2GB RAM and 1h for the whole procedure. BETA may run on the web server at Cistrome or may be downloaded.

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MendelianRandomization (tool)

RRID:SCR_025049

Software Mendelian randomization R package. Encodes several methods for performing Mendelian randomization analyses with summarized data.

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