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Wang, C.* ; Ni, W. ; Yao, Y. ; Just, A.* ; Heiss, J.* ; Wei, Y.* ; Gao, X.* ; Coull, B.A.* ; Kosheleva, A.* ; Baccarelli, A.A.* ; Peters, A. ; Schwartz, J.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.

EBioMedicine 63:103151 (2021)

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	Open Access Gold

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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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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords All-cause Death ; Cancer ; Competing Risk ; Dna Methylation Based Biomarkers Of Age Acceleration ; Myocardial Infarction ; Stroke; Competing Risks; Epigenetic Age; Air-pollution; Blood; Mortality; Predictors; Hazards; Disease

ISSN (print) / ISBN 2352-3964

e-ISSN 2352-3964

Journal EBioMedicine

Quellenangaben Volume: 63, Article Number: 103151

Publisher Elsevier

Publishing Place Amsterdam [u.a.]

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Epidemiology II (EPI2)

Grants State of Bavaria
Helmholtz Zentrum Munchen -German Research Center for Environmental Health - German Federal Ministry of Education and Research (BMBF)
HSPH-NIEHS Center for Environmental Health
National Institute of Environmental Health Sciences