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 Joehanes; Joel 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

doi:10.1186/s13059-015-0584-6

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 journal › Article › peer-review

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 (Δ_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 Δ_age and mortality. A 5-year higher Δ_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 Δ_age. A pedigree-based heritability analysis of Δ_age was conducted in a separate cohort. The heritability of Δ_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 language	English
Article number	25
Number of pages	12
Journal	Genome Biology
Volume	16
Early online date	30 Jan 2015
DOIs	https://doi.org/10.1186/s13059-015-0584-6
Publication status	Published - 30 Jan 2015

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DNA methylation age of blood predicts all-cause mortality in later life
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Centre for Cognitive Ageing and Cognitive Epidemiology Phase 2.
Maclullich, A.
1/09/13 → 31/08/19
Project: Research
RA2661 Centre for Cognitive Ageing and Cognitive Epidemiology Phase 2. Main Budget.
Deary, I., Gale, C., Holmes, M., Logie, P., Maclullich, A., Porteous, D., Seckl, J., Starr, J., Wardlaw, J. & Okely, J.
1/09/13 → 31/08/19
Project: Research
Disconnected Mind [Phase 2]
Wardlaw, J.
UK-based charities
1/01/11 → 31/03/16
Project: Research

Riccardo Marioni
- Centre for Genomic and Experimental Medicine
- Edinburgh Neuroscience
- School of Genetics and Cancer - Personal Chair of Molecular Epidemiology of Ageing
Person: Academic: Research Active

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, Article 25. https://doi.org/10.1186/s13059-015-0584-6

@article{353bbf69e3864788805d9cb18b41baeb,

title = "DNA methylation age of blood predicts all-cause mortality in later life",

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{\textquoteright}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.",

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

year = "2015",

month = jan,

day = "30",

doi = "10.1186/s13059-015-0584-6",

language = "English",

volume = "16",

journal = "Genome Biology",

issn = "1465-6906",

publisher = "BioMed Central",

}

Marioni, RE, Shah, S, McRae, AF, Chen, BH, Colicino, E, Harris, SE, Gibson, J, Henders, AK, Redmond, P, Cox, SR, Pattie, A, Corley, J , Murphy, L, Martin, NG, Montgomery, GW, Feinberg, AP, Fallin, MD, Multhaup, ML, Jaffe, AE, Joehanes, R, Schwartz, J, Just, AC, Lunetta, KL, Murabito, JM, Starr, JM, Horvath, S, Baccarelli, AA, Levy, D, Visscher, PM, Wray, NR & Deary, IJ 2015, 'DNA methylation age of blood predicts all-cause mortality in later life', Genome Biology, vol. 16, 25. https://doi.org/10.1186/s13059-015-0584-6

TY - JOUR

T1 - DNA methylation age of blood predicts all-cause mortality in later life

AU - Marioni, Riccardo E

AU - Shah, Sonia

AU - McRae, Allan F

AU - Chen, Brian H

AU - Colicino, Elena

AU - Harris, Sarah E

AU - Gibson, Jude

AU - Henders, Anjali K

AU - Redmond, Paul

AU - Cox, Simon R

AU - Pattie, Alison

AU - Corley, Janie

AU - Murphy, Lee

AU - Martin, Nicholas G

AU - Montgomery, Grant W

AU - Feinberg, Andrew P

AU - Fallin, M Daniele

AU - Multhaup, Michael L

AU - Jaffe, Andrew E

AU - Joehanes, Roby

AU - Schwartz, Joel

AU - Just, Allan C

AU - Lunetta, Kathryn L

AU - Murabito, Joanne M

AU - Starr, John M

AU - Horvath, Steve

AU - Baccarelli, Andrea A

AU - Levy, Daniel

AU - Visscher, Peter M

AU - Wray, Naomi R

AU - Deary, Ian J

PY - 2015/1/30

Y1 - 2015/1/30

N2 - 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.

AB - 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.

U2 - 10.1186/s13059-015-0584-6

DO - 10.1186/s13059-015-0584-6

M3 - Article

C2 - 25633388

SN - 1465-6906

VL - 16

JO - Genome Biology

JF - Genome Biology

M1 - 25

ER -

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

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Projects

Centre for Cognitive Ageing and Cognitive Epidemiology Phase 2.

RA2661 Centre for Cognitive Ageing and Cognitive Epidemiology Phase 2. Main Budget.

Disconnected Mind [Phase 2]

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Riccardo Marioni

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