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

被引：821

作者：

Marioni, Riccardo E. ^{[1
,2
,3
]}

Shah, Sonia ^{[3
,4
]}

McRae, Allan F. ^{[3
,4
]}

Chen, Brian H. ^{[5
,6
]}

Colicino, Elena ^{[7
]}

Harris, Sarah E. ^{[1
,2
]}

Gibson, Jude ^{[8
]}

Henders, Anjali K. ^{[9
]}

Redmond, Paul ^{[10
]}

Cox, Simon R. ^{[1
,10
]}

Pattie, Alison ^{[10
]}

Corley, Janie ^{[10
]}

Murphy, Lee ^{[8
]}

Martin, Nicholas G. ^{[9
]}

Montgomery, Grant W. ^{[9
]}

Feinberg, Andrew P. ^{[11
,12
,13
,14
,15
]}

Fallin, M. Daniele ^{[11
,16
]}

Multhaup, Michael L. ^{[11
]}

Jaffe, Andrew E. ^{[16
,17
]}

Joehanes, Roby ^{[5
,18
,19
]}

Schwartz, Joel ^{[7
,20
]}

Just, Allan C. ^{[7
]}

Lunetta, Kathryn L. ^{[5
,21
]}

Murabito, Joanne M. ^{[5
,22
]}

Starr, John M. ^{[1
,23
]}

Horvath, Steve ^{[24
,25
]}

Baccarelli, Andrea A. ^{[7
,20
]}

Levy, Daniel ^{[5
,6
]}

Visscher, Peter M. ^{[1
,3
,4
]}

Wray, Naomi R. ^{[3
]}

Deary, Ian J. ^{[1
,10
]}

机构：

[1] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9JZ, Midlothian, Scotland

[2] Univ Edinburgh, Inst Genet & Mol Med, Ctr Genom & Expt Med, Med Genet Sect, Edinburgh EH4 2XU, Midlothian, Scotland

[3] Univ Queensland, Queensland Brain Inst, Brisbane, Qld 4072, Australia

[4] Univ Queensland, Translat Res Inst, Diamantina Inst, Brisbane, Qld 4072, Australia

[5] NHLBIs Framingham Heart Study, Framingham, MA 01702 USA

[6] NHLBI, Div Intramural Res, Populat Sci Branch, Bethesda, MD 01702 USA

[7] Harvard TH Chan Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA

[8] Univ Edinburgh, Western Gen Hosp, Wellcome Trust Clin Res Facil, Edinburgh EH4 2XU, Midlothian, Scotland

[9] Queensland Inst Med Res Berghofer Med Res Inst, Brisbane, Qld 4029, Australia

[10] Univ Edinburgh, Dept Psychol, Edinburgh EH8 9JZ, Midlothian, Scotland

[11] Johns Hopkins Univ, Sch Med, Ctr Epigenet, Baltimore, MD 21205 USA

[12] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA

[13] Johns Hopkins Univ, Sch Med, Dept Mol Biol, Baltimore, MD 21205 USA

[14] Johns Hopkins Univ, Sch Med, Dept Genet, Baltimore, MD 21205 USA

[15] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA

[16] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD 21205 USA

[17] Lieber Inst Brain Dev, Baltimore, MD 21205 USA

[18] Harvard Univ, Sch Med, Boston, MA 02115 USA

[19] Hebrew Senior Life, Boston, MA 02131 USA

[20] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA

[21] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA

[22] Boston Univ, Sch Med, Dept Med, Sect Gen Internal Med, Boston, MA 02118 USA

[23] Univ Edinburgh, Alzheimer Scotland Dementia Res Ctr, Edinburgh EH8 9JZ, Midlothian, Scotland

[24] Univ Calif Los Angeles, David Geffen Sch Med, Gonda Res Ctr, Human Genet, Los Angeles, CA 90095 USA

[25] Univ Calif Los Angeles, Sch Publ Hlth, Biostat, Los Angeles, CA 90095 USA

来源：

GENOME BIOLOGY | 2015年 / 16卷

基金：

英国生物技术与生命科学研究理事会; 美国国家卫生研究院; 英国医学研究理事会; 英国惠康基金; 澳大利亚国家健康与医学研究理事会;

关键词：

TELOMERE LENGTH; HUMAN LONGEVITY; T-CELLS; INTELLIGENCE; ASSOCIATION; DEMENTIA; FAMILIES; DISEASE; TRAITS;

D O I：

10.1186/s13059-015-0584-6

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

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 (Delta(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 Delta(age) and mortality. A 5-year higher Delta(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 Delta(age). A pedigree-based heritability analysis of Delta(age) was conducted in a separate cohort. The heritability of Delta(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.

引用

页数：12

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