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Improved precision of epigenetic clock estimates across tissues and its implication for biological ageing
- Source :
- Genome Medicine, Vol 11, Iss 1, Pp 1-11 (2019), Genome Medicine, Zhang, Q, Vallerga, C L, Walker, R M, Lin, T, Henders, A K, Montgomery, G W, He, J, Fan, D, Fowdar, J, Kennedy, M, Pitcher, T, Pearson, J, Halliday, G, Kwok, J B, Hickie, I, Lewis, S, Anderson, T, Silburn, P A, Mellick, G D, Harris, S E, Redmond, P, Murray, A D, Porteous, D J, Haley, C S, Evans, K L, Mcintosh, A M, Yang, J, Gratten, J, Marioni, R E, Wray, N R, Deary, I J, Mcrae, A F & Visscher, P M 2019, ' Improved precision of epigenetic clock estimates across tissues and its implication for biological ageing ', Genome Medicine, vol. 11, no. 1, 54 . https://doi.org/10.1186/s13073-019-0667-1
- Publication Year :
- 2019
- Publisher :
- BMC, 2019.
-
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. Electronic supplementary material The online version of this article (10.1186/s13073-019-0667-1) contains supplementary material, which is available to authorized users.
- Subjects :
- 0301 basic medicine
Oncology
Epigenomics
medicine.medical_specialty
Aging
Epigenetic clock
lcsh:QH426-470
Age prediction
lcsh:Medicine
Epigenesis, Genetic
03 medical and health sciences
0302 clinical medicine
Internal medicine
Genetics
Medicine
Humans
Genetic Predisposition to Disease
Epigenetics
Mortality
Saliva
Molecular Biology
Genetics (clinical)
Proportional Hazards Models
DNA methylation
business.industry
Research
Confounding
lcsh:R
Reproducibility of Results
Small sample
Chronological age
3. Good health
Ageing
lcsh:Genetics
030104 developmental biology
Sample size determination
Organ Specificity
030220 oncology & carcinogenesis
Molecular Medicine
business
Birth cohort
Genome-Wide Association Study
Subjects
Details
- Language :
- English
- Volume :
- 11
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Genome Medicine
- Accession number :
- edsair.doi.dedup.....6e23aea39874f3892565dd03cfa18b71