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 journalArticle

Abstract

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 ({increment}age) 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 {increment}age and mortality. A 5-year higher {increment}age 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 {increment}age. A pedigree-based heritability analysis of {increment}age was conducted in a separate cohort. The heritability of {increment}age 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 (US)
Article number25
JournalGenome biology
Volume16
Issue number1
DOIs
StatePublished - Jan 30 2015

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Genetics
  • Cell Biology

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  • Cite this

    Marioni, R. E., Shah, S., McRae, A. F., Chen, B. H., Colicino, E., Harris, S. E., Gibson, J., Henders, A. K., Redmond, P., Cox, S. R., Pattie, A., Corley, J., Murphy, L., Martin, N. G., Montgomery, G. W., Feinberg, A. P., Fallin, M. D., Multhaup, M. L., Jaffe, A. E., ... Deary, I. J. (2015). DNA methylation age of blood predicts all-cause mortality in later life. Genome biology, 16(1), [25]. https://doi.org/10.1186/s13059-015-0584-6