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DNA methylation signature of chronic low-grade inflammation and its role in cardio-respiratory diseases |
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| Author: | Wielscher, Matthias1,2; Mandaviya, Pooja R.3,4; Kuehnel, Brigitte5; |
| Organizations: |
1Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England. 2Med Univ Vienna, Dept Dermatol, Vienna, Austria. 3Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
4Maastricht Univ, Maastricht Ctr Syst Biol MaCSBio, Maastricht, Netherlands.
5German Res Ctr Environm Hlth, Inst Epidemiol, Res Unit Mol Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Bavaria, Germany. 6Framingham Heart Dis Epidemiol Study, Framingham, MA USA. 7NHLBI, Populat Sci Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. 8German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany. 9Univ Bath, Dept Psychol, Bath, Avon, England. 10Univ Bristol, Bristol Med Sch, Med Res Council Integrat Epidemiol Unit, Bristol, Avon, England. 11Tampere Univ, Fac Med & Hlth Technol, Dept Clin Chem, Tampere, Finland. 12Tampere Univ, Fac Med & Hlth Technol, Finnish Cardiovasc Res Ctr, Tampere, Finland. 13Fimlab Labs, Dept Clin Chem, Tampere, Finland. 14Univ Freiburg, Inst Genet Epidemiol, Fac Med, Freiburg, Germany. 15Med Ctr Univ Freiburg, Freiburg, Germany. 16Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England. 17Chang Gung Univ, Dept Biomed Sci, Taoyuan, Taiwan. 18Univ Oulu, Fac Med, Ctr Life Course Hlth Res, Pentti Kaiteran Katu 1, Oulu, Finland. 19Univ Edinburgh, Ctr Genom & Expt Med, Edinburgh, Midlothian, Scotland. 20Univ Sassari, Dept Biomed Sci, Lab Biostat, Sassari, Italy. 21Imperial Coll London, MRC Ctr Environm & Hlth, Sch Publ Hlth, London, England. 22Fdn IRCCS Ist Nazl Tumori, Milan, Italy. 23Erasmus MC Univ Med Ctr, Dept Epidemiol, Rotterdam, Netherlands. 24Mashhad Univ Med Sci, Dept Genet, Mashhad, Iran. 25Univ Washington, Dept Med, Cardiovacular Hlth Res Unit, Seattle, WA USA. 26Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. 27Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. 28Lee Kong Chian Sch Med, Mandalay Rd, Singapore, Singapore. 29Univ Washington, Div Cardiol, Cardiovasc Hlth Res Unit, Seattle, WA USA. 30Univ Edinburgh, Dept Psychol, Lothian Birth Cohorts, Edinburgh, Midlothian, Scotland. 31Univ Cambridge, Sch Clin Med, MRC Epidemiol Unit, Cambridge, England. 32Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. 33Johns Hopkins Bloomberg Sch Publ Hlth, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA. 34Emory Univ, Sch Med, Dept Gynecol, Atlanta, GA USA. 35Emory Univ, Sch Med, Dept Psychiat, Atlanta, GA USA. 36Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA USA. 37Emory Univ, Sch Med, Winship Canc Inst, Dept Radiat Oncol, Atlanta, GA USA. 38Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England. 39Heinrich Heine Univ Dusseldorf, German Diabet Ctr, Leibniz Ctr Diabet Res, Inst Biometr & Epidemiol, Dusseldorf, Germany. 40Tech Univ Munich, Deutsch Herzzentrum Munchen, Munich, Germany. 41German Ctr Cardiovasc Res DZHK, Partner Site Munich Heart Alliance, Munich, Germany. 42Univ Ulm, Inst Epidemiol & Med Biometry, Ulm, Germany. 43Shandong Univ, Sch Publ Hlth, Dept Biostat, Jinan, Peoples R China. 44Tulane Univ, Dept Epidemiol, Sch Publ Hlth & Trop Med, New Orleans, LA 70118 USA. 45Univ Med Greifswald, Inst Community Med, Greifswald, Germany. 46DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, Greifswald, Germany. 47Univ Med Greifswald, Inst Clin Chem & Lab Med, Greifswald, Germany. 48Univ Med Greifswald, Dept Psychiat & Psychotherapy, Greifswald, Germany. 49Univ Med Greifswald, Dept Internal Med B, Greifswald, Germany. 50Univ Minnesota, Sch Publ Hlth, Div Biostat, Minneapolis, MN 55455 USA. 51Univ Tartu, Estonian Genome Ctr, Inst Genom, Tartu, Estonia. 52NIA, Translat Gerontol Branch, Biomed Res Ctr, NIH, Baltimore, MD 21224 USA. 53Univ Tartu, Inst Math & Stat, Tartu, Estonia. 54HudsonAlpha Inst Biotechnol, Huntsville, AL USA. 55Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Hanzepl 1, Groningen, Netherlands. 56Univ Med Ctr Utrecht, Dept Cardiol, Div Heart & Lungs, Utrecht, Netherlands. 57IRCCS NEUROMED, Dept Epidemiol & Prevent, Pozzilli, IS, Italy. 58Univ Insubria, Res Ctr Epidemiol & Prevent Med EPIMED, Dept Med & Surg, Varese Como, Italy. 59Citta Salute & Sci Hosp, Unit Canc Epidemiol, Turin, Italy. 60Ctr Canc Prevent, Turin, Italy. 61Univ Naples Federico II, Dipartimento Med Clin & Chirurg, Naples, Italy. 62Fdn IRCCS Ist Nazl Tumori, Epidemiol & Prevent Unit, Milan, Italy. 63Civ MPP Arezzo Hosp, Canc Registry & Histopathol Dept, ASP Ragusa, Ragusa, Italy. 64Univ Turin, Dept Med Sci, Turin, Italy. 65AOU Citta Salute & Sci Torino, Turin, Italy. 66Tampere Univ, Fac Med & Hlth Technol, Tampere, Finland. 67Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland. 68Turku Univ Hosp, Dept Clin Physiol & Nucl Med, Turku, Finland. 69Univ Turku, Ctr Populat Hlth Res, Turku, Finland. 70Turku Univ Hosp, Turku, Finland. 71Icahn Sch Med Mt Sinai, Dept Environm Med & Publ Hlth, New York, NY 10029 USA. 72Columbia Univ, Mailman Sch Publ Hlth, Dept Environm Hlth Sci, Lab Environm Epigenet, New York, NY USA. 73Columbia Univ, Dept Epidemiol, Lab Environm Epigenet, Mailman Sch Publ Hlth, New York, NY USA. 74Tampere Univ Hosp, Dept Clin Physiol, Tampere, Finland. 75Univ Oulu, Fac Med, Med Res Ctr, Res Unit Biomed, Oulu, Finland. 76Oulu Univ Hosp, Oulu, Finland. 77Poznan Univ Med Sci, Inst Pediat, Dept Gastroenterol & Metab, Poznan, Poland. 78Childrens Minnesota, Childrens Minnesota Res Inst, Minneapolis, MN USA. 79Emory Univ, Sch Med, Dept Human Genet, Atlanta, GA USA. 80Imperial Coll London, Natl Heart & Lung Inst, London, England. 81London North West Healthcare NHS Trust, Dept Cardiol, Ealing Hosp, Southall, Middx, England. 82Leiden Univ Med Ctr, Dept Biomed Data Sci, Mol Epidemiol, Leiden, Netherlands. 83Univ Texas Hlth Sci Ctr Houston, Human Genet Ctr, Houston, TX 77030 USA. 84Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA. 85Imperial Coll London, Imperial Biomed Res Ctr, London, England. 86Imperial Coll London, British Heart Fdn, Ctr Res Excellence, London, England. 87Heidelberg Univ, Network Aging Res, Heidelberg, Germany. 88Leiden Univ Med Ctr, Dept Med Stat & Bioinformat, Leiden, Netherlands. 89Imperial Coll London, UK Dementia Res Inst, London, England. 90Oulu Univ Hosp, Unit Primary Care, Oulu, Finland. 91Brunel Univ London, Coll Hlth & Life Sci, Dept Life Sci, London, England. |
| Format: | article |
| Version: | published version |
| Access: | open |
| Online Access: | PDF Full Text (PDF, 2.2 MB) |
| Persistent link: | http://urn.fi/urn:nbn:fi-fe2022110764776 |
| Language: | English |
| Published: |
Springer Nature,
2022
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| Publish Date: | 2022-11-07 |
| Description: |
AbstractWe 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. see all
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| Series: |
Nature communications |
| ISSN: | 2041-1723 |
| ISSN-E: | 2041-1723 |
| ISSN-L: | 2041-1723 |
| Volume: | 13 |
| Issue: | 1 |
| Article number: | 2408 |
| DOI: | 10.1038/s41467-022-29792-6 |
| OADOI: | https://oadoi.org/10.1038/s41467-022-29792-6 |
| Type of Publication: |
A1 Journal article – refereed |
| Field of Science: |
1182 Biochemistry, cell and molecular biology 3111 Biomedicine |
| Subjects: | |
| Funding: |
OR was supported by an UK Research and Innovation Future Leaders Fellowship (MR/S03532X/1). This study was partly supported by the European Commission grant to the LIFEPATH project (Horizon 2020 grant number 633666). The Airwave Health Monitoring Study was funded by the Home Office (2003-2018, grant number 780- TETRA) and is currently funded by the Medical Research Council/Economic & Social Research Council (grant number MR/R023484/1) with additional support from the National Institute for Health Research (NIHR) Imperial College Biomedical Research Centre. The Airwave Study uses the computing resources of the UK MEDical BIOinformatics partnership (UK MED-BIO supported by the Medical Research Council (MR/L01632X/1). We thank all Airwave participants for their contributions. PE is Director of the MRC Centre for Environment and Health and acknowledges support from the Medical Research Council (Mr/S019669/1). PE also acknowledges support from the Imperial College BHF Centre for Research Excellence (RE/18/4/34215) |
| Dataset Reference: |
The summary statistics from the meta-analyses are available on figshare website (https://doi.org/10.6084/m9.figshare.19188674.v1.) |
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https://doi.org/10.6084/m9.figshare.19188674.v1 |
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| Copyright information: |
© The Author(s) 2022. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
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https://creativecommons.org/licenses/by/4.0/ |