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DNA methylation signature of chronic low-grade inflammation and its role in cardio-respiratory diseases.
Wielscher, Matthias; Mandaviya, Pooja R; Kuehnel, Brigitte; Joehanes, Roby; Mustafa, Rima; Robinson, Oliver; Zhang, Yan; Bodinier, Barbara; Walton, Esther; Mishra, Pashupati P; Schlosser, Pascal; Wilson, Rory; Tsai, Pei-Chien; Palaniswamy, Saranya; Marioni, Riccardo E; Fiorito, Giovanni; Cugliari, Giovanni; Karhunen, Ville; Ghanbari, Mohsen; Psaty, Bruce M; Loh, Marie; Bis, Joshua C; Lehne, Benjamin; Sotoodehnia, Nona; Deary, Ian J; Chadeau-Hyam, Marc; Brody, Jennifer A; Cardona, Alexia; Selvin, Elizabeth; Smith, Alicia K; Miller, Andrew H; Torres, Mylin A; Marouli, Eirini; Gào, Xin; van Meurs, Joyce B J; Graf-Schindler, Johanna; Rathmann, Wolfgang; Koenig, Wolfgang; Peters, Annette; Weninger, Wolfgang; Farlik, Matthias; Zhang, Tao; Chen, Wei; Xia, Yujing; Teumer, Alexander; Nauck, Matthias; Grabe, Hans J; Doerr, Macus; Lehtimäki, Terho; Guan, Weihua.
Afiliación
  • Wielscher M; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. matthias.wielscher@meduniwien.ac.at.
  • Mandaviya PR; Department of Dermatology, Medical University of Vienna, Vienna, Austria. matthias.wielscher@meduniwien.ac.at.
  • Kuehnel B; Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.
  • Joehanes R; Maastricht Centre for Systems Biology (MaCSBio), Maastricht University, Maastricht, The Netherlands.
  • Mustafa R; Research Unit Molecular Epidemiology, Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Bavaria, Germany.
  • Robinson O; Framingham Heart Study, Framingham, MA, USA.
  • Zhang Y; Population Sciences Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
  • Bodinier B; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
  • Walton E; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
  • Mishra PP; Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany.
  • Schlosser P; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
  • Wilson R; Department of Psychology, University of Bath, Bath, UK.
  • Tsai PC; Medical Research Council Integrative Epidemiology Unit, Bristol Medical School, University of Bristol, Bristol, UK.
  • Palaniswamy S; Department of Clinical Chemistry, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
  • Marioni RE; Finnish Cardiovascular Research Centre, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
  • Fiorito G; Department of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland.
  • Cugliari G; Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center - University of Freiburg, Freiburg, Germany.
  • Karhunen V; Research Unit Molecular Epidemiology, Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Bavaria, Germany.
  • Ghanbari M; Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
  • Psaty BM; Department of Biomedical Sciences, Chang Gung University, Taoyuan City, Taiwan.
  • Loh M; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
  • Bis JC; Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Pentti Kaiteran katu 1, Linnanmaa, Oulu, Finland.
  • Lehne B; Centre for Genomic and Experimental Medicine, University of Edinburgh, Edinburgh, UK.
  • Sotoodehnia N; Laboratory of Biostatistics, Department of Biomedical Sciences, University of Sassari, Sassari, Italy.
  • Deary IJ; MRC Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.
  • Chadeau-Hyam M; Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
  • Brody JA; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
  • Cardona A; Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
  • Selvin E; Department of Genetics, Mashhad University of Medical Sciences, Mashhad, Iran.
  • Smith AK; Cardiovacular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.
  • Miller AH; Department of Health Services, University of Washington, Seattle, WA, USA.
  • Torres MA; Department of Epidemiology, University of Washington, Seattle, WA, USA.
  • Marouli E; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
  • Gào X; Lee Kong Chian School of Medicine, Mandalay Road, Singapore, Singapore.
  • van Meurs JBJ; Cardiovascular Health Research Unit, Division of Cardiology, University of Washington, Seattle, WA, USA.
  • Graf-Schindler J; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
  • Rathmann W; Cardiovascular Health Research Unit, Division of Cardiology, University of Washington, Seattle, WA, USA.
  • Koenig W; Lothian Birth Cohorts, Department of Psychology, University of Edinburgh, Edinburgh, UK.
  • Peters A; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
  • Weninger W; Cardiovascular Health Research Unit, Division of Cardiology, University of Washington, Seattle, WA, USA.
  • Farlik M; MRC Epidemiology Unit, School of Clinical Medicine, University of Cambridge, Cambridge, UK.
  • Zhang T; Dept. of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
  • Chen W; Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
  • Xia Y; Departments of Gynecology and Obstetrics & Psychiatry and Behavioral Science, Emory University School of Medicine, Atlanta, GA, USA.
  • Teumer A; Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia.
  • Nauck M; Department of Radiation Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA.
  • Grabe HJ; William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
  • Doerr M; Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany.
  • Lehtimäki T; Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.
  • Guan W; Research Unit Molecular Epidemiology, Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Bavaria, Germany.
Nat Commun ; 13(1): 2408, 2022 05 03.
Article en En | MEDLINE | ID: mdl-35504910
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Metilación de ADN / Inflamación Tipo de estudio: Clinical_trials Límite: Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2022 Tipo del documento: Article País de afiliación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Metilación de ADN / Inflamación Tipo de estudio: Clinical_trials Límite: Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2022 Tipo del documento: Article País de afiliación: Reino Unido