DNA methylation age of blood predicts all-cause mortality in later life

Riccardo E Marioni, Sonia Shah, Allan F McRae, Brian H Chen, Elena Colicino, Sarah E Harris, Jude Gibson, Anjali K Henders, Paul Redmond, Simon R Cox, Alison Pattie, Janie Corley, Lee Murphy, Nicholas G Martin, Grant W Montgomery, Andrew P Feinberg, M Daniele Fallin, Michael L Multhaup, Andrew E Jaffe, Roby JoehanesJoel Schwartz, Allan C Just, Kathryn L Lunetta, Joanne M Murabito, John M Starr, Steve Horvath, Andrea A Baccarelli, Daniel Levy, Peter M Visscher, Naomi R Wray, Ian J Deary

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Background: DNA methylation levels change with age. Recent studies have identified biomarkers of chronological age based on DNA methylation levels. It is not yet known whether DNA methylation age captures aspects of biological age.

Results: Here we test whether differences between people’s chronological ages and estimated ages, DNA methylation age, predict all-cause mortality in later life. The difference between DNA methylation age and chronological age (Δage) was calculated in four longitudinal cohorts of older people. Meta-analysis of proportional hazards models from the four cohorts was used to determine the association between Δage and mortality. A 5-year higher Δage is associated with a 21% higher mortality risk, adjusting for age and sex. After further adjustments for childhood IQ, education, social class, hypertension, diabetes, cardiovascular disease, and APOE e4 status, there is a 16% increased mortality risk for those with a 5-year higher Δage. A pedigree-based heritability analysis of Δage was conducted in a separate cohort. The heritability of Δage was 0.43.

Conclusions:DNA methylation-derived measures of accelerated aging are heritable traits that predict mortality independently of health status, lifestyle factors, and known genetic factors.

Original languageEnglish
Article number25
Number of pages12
JournalGenome Biology
Volume16
Early online date30 Jan 2015
DOIs
Publication statusPublished - 30 Jan 2015

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