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

Citations Over TimeTop 1% of 2017 papers

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.

Related Papers

• → Maternal care, the epigenome and phenotypic differences in behavior(2007)265 cited
• → Nutrition and the Epigenome(2012)33 cited
• → Nutrition, epigenetics and health through life(2017)14 cited
• → Cause and effect in epigenetics – where lies the truth, and how can experiments reveal it?(2020)4 cited
• → The Ability of Nutrition to Mitigate Epigenetic Drift: A Novel Look at Regulating Gene Expression(2021)1 cited