Epigenetics meets proteomics in an epigenome-wide association study with circulating blood plasma protein traits
Nature Communications, vol. 11, pp. 15
Abstract
DNA methylation and blood circulating proteins have been associated with many complex disorders, but the underlying disease-causing mechanisms often remain unclear. Here, we report an epigenome-wide association study of 1123 proteins from 944 participants of the KORA population study and replication in a multi-ethnic cohort of 344 individuals. We identify 98 CpG-protein associations (pQTMs) at a stringent Bonferroni level of significance. Overlapping associations with transcriptomics, metabolomics, and clinical endpoints suggest implication of processes related to chronic low-grade inflammation, including a network involving methylation of NLRC5, a regulator of the inflammasome, and associated pQTMs implicating key proteins of the immune system, such as CD48, CD163, CXCL10, CXCL11, LAG3, FCGR3B, and B2M. Our study links DNA methylation to disease endpoints via intermediate proteomics phenotypes and identifies correlative networks that may eventually be targeted in a personalized approach of chronic low-grade inflammation.
Authors 20
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Weill Cornell Medical College in Qatar · Weill Cornell Medicine · Virginia Tech
Affiliation as printed
Computer Engineering Department, Virginia Tech, Blacksburg, VA, USA
Department of Physiology and Biophysics, Weill Cornell Medicine-Qatar, Doha, Qatar
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Affiliation as printed
Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Bavaria, Germany
Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Bavaria, Germany
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Helmholtz Munich · German Centre for Cardiovascular Research
Affiliation as printed
German Centre for Cardiovascular Research (DZHK), partner site Munich Heart Alliance, Munich, Germany
Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Bavaria, Germany
Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Bavaria, Germany
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Weill Cornell Medical College in Qatar · Weill Cornell Medicine
Affiliation as printed
Department of Physiology and Biophysics, Weill Cornell Medicine-Qatar, Doha, Qatar
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Weill Cornell Medical College in Qatar · Weill Cornell Medicine
Affiliation as printed
Department of Physiology and Biophysics, Weill Cornell Medicine-Qatar, Doha, Qatar
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Weill Cornell Medical College in Qatar · Weill Cornell Medicine
Affiliation as printed
Department of Physiology and Biophysics, Weill Cornell Medicine-Qatar, Doha, Qatar
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Weill Cornell Medical College in Qatar · Weill Cornell Medicine
Affiliation as printed
Proteomics Core, Weill Cornell Medicine-Qatar, Doha, Qatar
Proteomics Core, Weill Cornell Medicine‐Qatar, Doha, Qatar
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Weill Cornell Medical College in Qatar · Weill Cornell Medicine
Affiliation as printed
Proteomics Core, Weill Cornell Medicine-Qatar, Doha, Qatar
Proteomics Core, Weill Cornell Medicine‐Qatar, Doha, Qatar
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Weill Cornell Medical College in Qatar · Weill Cornell Medicine
Affiliation as printed
Genomics Core, Weill Cornell Medicine-Qatar, Doha, Qatar
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Weill Cornell Medical College in Qatar · Weill Cornell Medicine
Affiliation as printed
Genomics Core, Weill Cornell Medicine-Qatar, Doha, Qatar
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Helmholtz Munich · German Centre for Cardiovascular Research · Institut für Humangenetik · Technical University of Munich
Affiliation as printed
German Centre for Cardiovascular Research (DZHK), partner site Munich Heart Alliance, Munich, Germany
Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
Institute of Human Genetics, Technical University Munich, Munich, Germany
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Affiliation as printed
Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Bavaria, Germany
Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Bavaria, Germany
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Helmholtz Munich · Ludwig-Maximilians-Universität München
Affiliation as printed
Chair of Genetic Epidemiology, IBE, Faculty of Medicine, LMU Munich, Munich, Germany
Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
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Helmholtz Munich · German Centre for Cardiovascular Research
Affiliation as printed
German Centre for Cardiovascular Research (DZHK), partner site Munich Heart Alliance, Munich, Germany
Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Bavaria, Germany
Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Bavaria, Germany
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Leiden University · Leiden University Medical Center
Affiliation as printed
Department of Clinical Epidemiology, Leiden University Medical Centre, Leiden, The Netherlands
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Max Planck Institute for Heart and Lung Research · German Centre for Cardiovascular Research
Affiliation as printed
German Centre for Cardiovascular Research (DZHK), partner site Rhine-Main, Max Planck Institute of Heart and Lung Research, Bad Nauheim, Germany
Scientific Service Group Biomolecular Mass Spectrometry, Max Planck Institute for Heart and Lung Research, W.G. Kerckhoff Institute, Bad Nauheim, Germany
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Weill Cornell Medical College in Qatar · Weill Cornell Medicine
Affiliation as printed
Genomics Core, Weill Cornell Medicine-Qatar, Doha, Qatar
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Helmholtz Munich · German Centre for Cardiovascular Research
Affiliation as printed
German Centre for Cardiovascular Research (DZHK), partner site Munich Heart Alliance, Munich, Germany
Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Bavaria, Germany
Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Bavaria, Germany
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Helmholtz Munich · German Centre for Cardiovascular Research
Affiliation as printed
German Centre for Cardiovascular Research (DZHK), partner site Munich Heart Alliance, Munich, Germany
Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Bavaria, Germany
Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Bavaria, Germany
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Karsten Suhre corresponding
Weill Cornell Medical College in Qatar · Weill Cornell Medicine
Affiliation as printed
Department of Physiology and Biophysics, Weill Cornell Medicine-Qatar, Doha, Qatar. kas2049@qatar-med.cornell.edu
Department of Physiology and Biophysics, Weill Cornell Medicine-Qatar, Doha, Qatar
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