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DNA methylation signatures in peripheral blood strongly predict all-cause mortality.
Nat. Commun. 8:14617 (2017)
DNA methylation (DNAm) has been revealed to play a role in various diseases. Here we performed epigenome-wide screening and validation to identify mortality-related DNAm signatures in a general population-based cohort with up to 14 years follow-up. In the discovery panel in a case-cohort approach, 11,063 CpGs reach genome-wide significance (FDR<0.05). 58 CpGs, mapping to 38 well-known disease-related genes and 14 intergenic regions, are confirmed in a validation panel. A mortality risk score based on ten selected CpGs exhibits strong association with all-cause mortality, showing hazard ratios (95% CI) of 2.16 (1.10-4.24), 3.42 (1.81-6.46) and 7.36 (3.69-14.68), respectively, for participants with scores of 1, 2-5 and 5+ compared with a score of 0. These associations are confirmed in an independent cohort and are independent from the 'epigenetic clock'. In conclusion, DNAm of multiple disease-related genes are strongly linked to mortality outcomes. The DNAm-based risk score might be informative for risk assessment and stratification.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Epigenome-wide Association; Breast-cancer Cells; F2rl3 Methylation; Gene-expression; Cpg Sites; Cardiovascular Mortality; Epigenetic Clock; Telomere Length; Health Research; Cox Model
ISSN (print) / ISBN
2041-1723
e-ISSN
2041-1723
Journal
Nature Communications
Quellenangaben
Volume: 8,
Article Number: 14617
Publisher
Nature Publishing Group
Publishing Place
London
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Epidemiology II (EPI2)