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Nat Commun. 2017 Mar 17;8:14617. doi: 10.1038/ncomms14617.

DNA methylation signatures in peripheral blood strongly predict all-cause mortality.

Author information

1
Division of Clinical Epidemiology and Aging Research, German Research Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
2
Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Center for Environmental Health, D-85764 Neuherberg, Germany.
3
Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, D-85764 Neuherberg, Germany.
4
Network Ageing Research, University of Heidelberg, Bergheimer Strasse 20, D-69115 Heidelberg, Germany.
5
Saarland Cancer Registry, Präsident Baltz Strasse 5, D-66119 Saarbrücken, Germany.
6
Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Im Neuenheimer Feld 460, D-69120 Heidelberg, Germany.
7
German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany.

Abstract

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.

PMID:
28303888
PMCID:
PMC5357865
DOI:
10.1038/ncomms14617
[Indexed for MEDLINE]
Free PMC Article

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