DNA methylation-based biomarkers of age acceleration and all-cause death, myocardial infarction, stroke, and cancer in two cohorts: The NAS, and KORA F4

BACKGROUND: DNA methylation (DNAm) may play a role in age-related outcomes. It is not yet known which DNAm-based biomarkers of age acceleration (BoAA) has the strongest association with age-related endpoints. METHODS: We collected the blood samples from two independent cohorts: the Normative Ageing...

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Autores principales: Wang, Cuicui, Ni, Wenli, Yao, Yueli, Just, Allan, Heiss, Jonathan, Wei, Yaguang, Gao, Xu, Coull, Brent A., Kosheleva, Anna, Baccarelli, Andrea A., Peters, Annette, Schwartz, Joel D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724153/
https://www.ncbi.nlm.nih.gov/pubmed/33279859
http://dx.doi.org/10.1016/j.ebiom.2020.103151
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author Wang, Cuicui
Ni, Wenli
Yao, Yueli
Just, Allan
Heiss, Jonathan
Wei, Yaguang
Gao, Xu
Coull, Brent A.
Kosheleva, Anna
Baccarelli, Andrea A.
Peters, Annette
Schwartz, Joel D.
author_facet Wang, Cuicui
Ni, Wenli
Yao, Yueli
Just, Allan
Heiss, Jonathan
Wei, Yaguang
Gao, Xu
Coull, Brent A.
Kosheleva, Anna
Baccarelli, Andrea A.
Peters, Annette
Schwartz, Joel D.
author_sort Wang, Cuicui
collection PubMed
description BACKGROUND: DNA methylation (DNAm) may play a role in age-related outcomes. It is not yet known which DNAm-based biomarkers of age acceleration (BoAA) has the strongest association with age-related endpoints. METHODS: We collected the blood samples from two independent cohorts: the Normative Ageing Study, and the Cooperative Health Research in the Region of Augsburg cohort. We measured epigenome-wide DNAm level, and generated five DNAm BoAA at baseline. We used Cox proportional hazards model to analyze the relationships between BoAA and all-cause death. We applied the Fine and Gray competing risk model to estimate the risk of BoAA on myocardial infarction (MI), stroke, and cancer, accounting for death of other reasons as the competing risks. We used random-effects meta-analyses to pool the individual results, with adjustment for multiple testing. FINDINGS: The mean chronological ages in the two cohorts were 74, and 61, respectively. Baseline GrimAgeAccel, and DNAm-related mortality risk score (DNAmRS) both had strong associations with all-cause death, MI, and stroke, independent from chronological age. For example, a one standard deviation (SD) increment in GrimAgeAccel was significantly associated with increased risk of all-cause death [hazard ratio (HR): 2.01; 95% confidence interval (CI), 1.15, 3.50], higher risk of MI (HR: 1.44; 95% CI, 1.16, 1.79), and elevated risk of stroke (HR: 1.42; 95% CI, 1.06, 1.91). There were no associations between any BoAA and cancer. INTERPRETATION: From the public health perspective, GrimAgeAccel is the most useful tool for identifying at-risk elderly, and evaluating the efficacy of anti-aging interventions. FUNDING: National Institute of Environmental Health Sciences of U.S., Harvard Chan-NIEHS Center for Environmental Health, German Federal Ministry of Education and Research, and the State of Bavaria in Germany.
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spelling pubmed-77241532020-12-13 DNA methylation-based biomarkers of age acceleration and all-cause death, myocardial infarction, stroke, and cancer in two cohorts: The NAS, and KORA F4 Wang, Cuicui Ni, Wenli Yao, Yueli Just, Allan Heiss, Jonathan Wei, Yaguang Gao, Xu Coull, Brent A. Kosheleva, Anna Baccarelli, Andrea A. Peters, Annette Schwartz, Joel D. EBioMedicine Research Paper BACKGROUND: DNA methylation (DNAm) may play a role in age-related outcomes. It is not yet known which DNAm-based biomarkers of age acceleration (BoAA) has the strongest association with age-related endpoints. METHODS: We collected the blood samples from two independent cohorts: the Normative Ageing Study, and the Cooperative Health Research in the Region of Augsburg cohort. We measured epigenome-wide DNAm level, and generated five DNAm BoAA at baseline. We used Cox proportional hazards model to analyze the relationships between BoAA and all-cause death. We applied the Fine and Gray competing risk model to estimate the risk of BoAA on myocardial infarction (MI), stroke, and cancer, accounting for death of other reasons as the competing risks. We used random-effects meta-analyses to pool the individual results, with adjustment for multiple testing. FINDINGS: The mean chronological ages in the two cohorts were 74, and 61, respectively. Baseline GrimAgeAccel, and DNAm-related mortality risk score (DNAmRS) both had strong associations with all-cause death, MI, and stroke, independent from chronological age. For example, a one standard deviation (SD) increment in GrimAgeAccel was significantly associated with increased risk of all-cause death [hazard ratio (HR): 2.01; 95% confidence interval (CI), 1.15, 3.50], higher risk of MI (HR: 1.44; 95% CI, 1.16, 1.79), and elevated risk of stroke (HR: 1.42; 95% CI, 1.06, 1.91). There were no associations between any BoAA and cancer. INTERPRETATION: From the public health perspective, GrimAgeAccel is the most useful tool for identifying at-risk elderly, and evaluating the efficacy of anti-aging interventions. FUNDING: National Institute of Environmental Health Sciences of U.S., Harvard Chan-NIEHS Center for Environmental Health, German Federal Ministry of Education and Research, and the State of Bavaria in Germany. Elsevier 2020-12-03 /pmc/articles/PMC7724153/ /pubmed/33279859 http://dx.doi.org/10.1016/j.ebiom.2020.103151 Text en © 2020 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Paper
Wang, Cuicui
Ni, Wenli
Yao, Yueli
Just, Allan
Heiss, Jonathan
Wei, Yaguang
Gao, Xu
Coull, Brent A.
Kosheleva, Anna
Baccarelli, Andrea A.
Peters, Annette
Schwartz, Joel D.
DNA methylation-based biomarkers of age acceleration and all-cause death, myocardial infarction, stroke, and cancer in two cohorts: The NAS, and KORA F4
title DNA methylation-based biomarkers of age acceleration and all-cause death, myocardial infarction, stroke, and cancer in two cohorts: The NAS, and KORA F4
title_full DNA methylation-based biomarkers of age acceleration and all-cause death, myocardial infarction, stroke, and cancer in two cohorts: The NAS, and KORA F4
title_fullStr DNA methylation-based biomarkers of age acceleration and all-cause death, myocardial infarction, stroke, and cancer in two cohorts: The NAS, and KORA F4
title_full_unstemmed DNA methylation-based biomarkers of age acceleration and all-cause death, myocardial infarction, stroke, and cancer in two cohorts: The NAS, and KORA F4
title_short DNA methylation-based biomarkers of age acceleration and all-cause death, myocardial infarction, stroke, and cancer in two cohorts: The NAS, and KORA F4
title_sort dna methylation-based biomarkers of age acceleration and all-cause death, myocardial infarction, stroke, and cancer in two cohorts: the nas, and kora f4
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724153/
https://www.ncbi.nlm.nih.gov/pubmed/33279859
http://dx.doi.org/10.1016/j.ebiom.2020.103151
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