Dataset Information

Improved precision of epigenetic clock estimates across tissues and its implication for biological ageing.

ABSTRACT:

Background

DNA methylation changes with age. Chronological age predictors built from DNA methylation are termed 'epigenetic clocks'. The deviation of predicted age from the actual age ('age acceleration residual', AAR) has been reported to be associated with death. However, it is currently unclear how a better prediction of chronological age affects such association.

Methods

In this study, we build multiple predictors based on training DNA methylation samples selected from 13,661 samples (13,402 from blood and 259 from saliva). We use the Lothian Birth Cohorts of 1921 (LBC1921) and 1936 (LBC1936) to examine whether the association between AAR (from these predictors) and death is affected by (1) improving prediction accuracy of an age predictor as its training sample size increases (from 335 to 12,710) and (2) additionally correcting for confounders (i.e., cellular compositions). In addition, we investigated the performance of our predictor in non-blood tissues.

Results

We found that in principle, a near-perfect age predictor could be developed when the training sample size is sufficiently large. The association between AAR and mortality attenuates as prediction accuracy increases. AAR from our best predictor (based on Elastic Net, https://github.com/qzhang314/DNAm-based-age-predictor ) exhibits no association with mortality in both LBC1921 (hazard ratio = 1.08, 95% CI 0.91-1.27) and LBC1936 (hazard ratio = 1.00, 95% CI 0.79-1.28). Predictors based on small sample size are prone to confounding by cellular compositions relative to those from large sample size. We observed comparable performance of our predictor in non-blood tissues with a multi-tissue-based predictor.

Conclusions

This study indicates that the epigenetic clock can be improved by increasing the training sample size and that its association with mortality attenuates with increased prediction of chronological age.

SUBMITTER: Zhang Q

PROVIDER: S-EPMC6708158 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Publications

Improved precision of epigenetic clock estimates across tissues and its implication for biological ageing.

Zhang Qian Q Vallerga Costanza L CL Walker Rosie M RM Lin Tian T Henders Anjali K AK Montgomery Grant W GW He Ji J Fan Dongsheng D Fowdar Javed J Kennedy Martin M Pitcher Toni T Pearson John J Halliday Glenda G Kwok John B JB Hickie Ian I Lewis Simon S Anderson Tim T Silburn Peter A PA Mellick George D GD Harris Sarah E SE Redmond Paul P Murray Alison D AD Porteous David J DJ Haley Christopher S CS Evans Kathryn L KL McIntosh Andrew M AM Yang Jian J Gratten Jacob J Marioni Riccardo E RE Wray Naomi R NR Deary Ian J IJ McRae Allan F AF Visscher Peter M PM

Genome medicine 20190823 1

<h4>Background</h4>DNA methylation changes with age. Chronological age predictors built from DNA methylation are termed 'epigenetic clocks'. The deviation of predicted age from the actual age ('age acceleration residual', AAR) has been reported to be associated with death. However, it is currently unclear how a better prediction of chronological age affects such association.<h4>Methods</h4>In this study, we build multiple predictors based on training DNA methylation samples selected from 13,661 ...[more]

PMID: 31443728

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Dataset Information

Improved precision of epigenetic clock estimates across tissues and its implication for biological ageing.

Background

Methods

Results

Conclusions

Publications

Improved precision of epigenetic clock estimates across tissues and its implication for biological ageing.

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