DNAm-based signatures of accelerated aging and mortality in blood are associated with low renal function.

Autor:	Matías-García PR; TUM School of Medicine, Technical University of Munich, Munich, Germany. pamela.matias@helmholtz-muenchen.de.; Research Unit Molecular Epidemiology, Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich/Neuherberg, Germany. pamela.matias@helmholtz-muenchen.de.; Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich/Neuherberg, Germany. pamela.matias@helmholtz-muenchen.de.; German Center for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany. pamela.matias@helmholtz-muenchen.de., Ward-Caviness CK; Center for Public Health and Environmental Assessment, US Environmental Protection Agency, Chapel Hill, NC, USA., Raffield LM; Department of Genetics, University of North Carolina, Chapel Hill, NC, USA., Gao X; Laboratory of Precision Environmental Health, Mailman School of Public Health, Columbia University, New York, NY, USA., Zhang Y; Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany., Wilson R; Research Unit Molecular Epidemiology, Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich/Neuherberg, Germany.; Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich/Neuherberg, Germany., Gào X; Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany., Nano J; Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich/Neuherberg, Germany.; German Center for Diabetes Research (DZD), Neuherberg, Germany., Bostom A; Center For Primary Care and Prevention, Memorial Hospital of Rhode Island, Pawtucket, RI, USA., Colicino E; Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Correa A; Departments of Medicine and Pediatrics, University of Mississippi Medical Center, Jackson, MS, USA., Coull B; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA., Eaton C; Center For Primary Care and Prevention, Memorial Hospital of Rhode Island, Pawtucket, RI, USA.; Department of Family Medicine, Warren Alpert Medical School, Brown University, Providence, RI, USA., Hou L; Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA., Just AC; Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Kunze S; Research Unit Molecular Epidemiology, Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich/Neuherberg, Germany.; Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich/Neuherberg, Germany., Lange L; Department of Medicine, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA., Lange E; Department of Medicine, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA., Lin X; Veterans Affairs Normative Aging Study, Veterans Affairs Boston Healthcare System, Department of Medicine, Boston University School of Medicine, Boston, MA, USA., Liu S; Department of Epidemiology, School of Public Health, Brown University, Providence, RI, USA., Nwanaji-Enwerem JC; Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA., Reiner A; Department of Epidemiology, University of Washington, Seattle, WA, USA., Shen J; Department of Population Health Sciences, School of Medicine, University of Utah, Salt Lake City, UT, USA., Schöttker B; Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Network Aging Research, University of Heidelberg, Heidelberg, Germany., Vokonas P; Veterans Affairs Normative Aging Study, Veterans Affairs Boston Healthcare System, Department of Medicine, Boston University School of Medicine, Boston, MA, USA., Zheng Y; Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA., Young B; Nephrology, Hospital and Specialty Medicine and Center for Innovation for Veteran-Centered and Value Driven Care, Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA.; Division of Nephrology, Kidney Research Institute, University of Washington, Seattle, WA, USA., Schwartz J; Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA., Horvath S; Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA., Lu A; Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA., Whitsel EA; Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.; Department of Medicine, School of Medicine, University of North Carolina, Chapel Hill, NC, USA., Koenig W; German Center for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany.; Deutsches Herzzentrum München, Technische Universität München, Munich, Germany.; Institute of Epidemiology and Medical Biometry, University of Ulm, Ulm, Germany., Adamski J; Research Unit Molecular Endocrinology and Metabolism, Genome Analysis Center, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich/Neuherberg, Germany.; Chair for Experimental Genetics, Technical University of Munich, Freising-Weihenstephan, Germany.; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Winkelmann J; Institute of Neurogenomics, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich/Neuherberg, Germany.; Chair Neurogenetics, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.; Institute of Human Genetics, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany., Brenner H; Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Network Aging Research, University of Heidelberg, Heidelberg, Germany., Baccarelli AA; Laboratory of Precision Environmental Health, Mailman School of Public Health, Columbia University, New York, NY, USA., Gieger C; Research Unit Molecular Epidemiology, Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich/Neuherberg, Germany.; Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich/Neuherberg, Germany., Peters A; Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich/Neuherberg, Germany.; German Center for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany.; German Center for Diabetes Research (DZD), Neuherberg, Germany., Franceschini N; Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA., Waldenberger M; Research Unit Molecular Epidemiology, Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich/Neuherberg, Germany. waldenberger@helmholtz-muenchen.de.; Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich/Neuherberg, Germany. waldenberger@helmholtz-muenchen.de.; German Center for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany. waldenberger@helmholtz-muenchen.de.
Jazyk:	angličtina
Zdroj:	Clinical epigenetics [Clin Epigenetics] 2021 Jun 02; Vol. 13 (1), pp. 121. Date of Electronic Publication: 2021 Jun 02.
DOI:	10.1186/s13148-021-01082-w
Abstrakt:	Background: The difference between an individual's chronological and DNA methylation predicted age (DNAmAge), termed DNAmAge acceleration (DNAmAA), can capture life-long environmental exposures and age-related physiological changes reflected in methylation status. Several studies have linked DNAmAA to morbidity and mortality, yet its relationship with kidney function has not been assessed. We evaluated the associations between seven DNAm aging and lifespan predictors (as well as GrimAge components) and five kidney traits (estimated glomerular filtration rate [eGFR], urine albumin-to-creatinine ratio [uACR], serum urate, microalbuminuria and chronic kidney disease [CKD]) in up to 9688 European, African American and Hispanic/Latino individuals from seven population-based studies. Results: We identified 23 significant associations in our large trans-ethnic meta-analysis (p < 1.43E-03 and consistent direction of effect across studies). Age acceleration measured by the Extrinsic and PhenoAge estimators, as well as Zhang's 10-CpG epigenetic mortality risk score (MRS), were associated with all parameters of poor kidney health (lower eGFR, prevalent CKD, higher uACR, microalbuminuria and higher serum urate). Six of these associations were independently observed in European and African American populations. MRS in particular was consistently associated with eGFR (β =  - 0.12, 95% CI = [- 0.16, - 0.08] change in log-transformed eGFR per unit increase in MRS, p = 4.39E-08), prevalent CKD (odds ratio (OR) = 1.78 [1.47, 2.16], p = 2.71E-09) and higher serum urate levels (β = 0.12 [0.07, 0.16], p = 2.08E-06). The "first-generation" clocks (Hannum, Horvath) and GrimAge showed different patterns of association with the kidney traits. Three of the DNAm-estimated components of GrimAge, namely adrenomedullin, plasminogen-activation inhibition 1 and pack years, were positively associated with higher uACR, serum urate and microalbuminuria. Conclusion: DNAmAge acceleration and DNAm mortality predictors estimated in whole blood were associated with multiple kidney traits, including eGFR and CKD, in this multi-ethnic study. Epigenetic biomarkers which reflect the systemic effects of age-related mechanisms such as immunosenescence, inflammaging and oxidative stress may have important mechanistic or prognostic roles in kidney disease. Our study highlights new findings linking kidney disease to biological aging, and opportunities warranting future investigation into DNA methylation biomarkers for prognostic or risk stratification in kidney disease.
Databáze:	MEDLINE
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