DNA methylation GrimAge version 2

Ake T Lu; Alexandra M. Binder; Joshua Zhang; Qi Yan; Alex P Reiner; Simon R. Cox; Janie Corley; Sarah Harris; Pei-Lun Kuo; Ann Zenobia Moore; Stefania Bandinelli; James Stewart; Cuicui Wang; Elissa J Hamlat; Elissa S. Epel; Joel Schwartz; Eric A Whitsel; Adolfo Correa; Luigi Ferrucci; Riccardo E Marioni; Steve Horvath

doi:10.18632/aging.204434

DNA methylation GrimAge version 2

Ake T Lu, Alexandra M. Binder, Joshua Zhang, Qi Yan, Alex P Reiner, Simon R. Cox, Janie Corley, Sarah Harris, Pei-Lun Kuo, Ann Zenobia Moore, Stefania Bandinelli, James Stewart, Cuicui Wang, Elissa J Hamlat, Elissa S. Epel, Joel Schwartz, Eric A Whitsel, Adolfo Correa, Luigi Ferrucci, Riccardo E MarioniSteve Horvath

Research output: Contribution to journal › Article › peer-review

Abstract

We previously described a DNA methylation (DNAm) based biomarker of human mortality risk DNAm GrimAge. Here we describe version 2 of GrimAge (trained on individuals aged between 40 and 92) which leverages two new DNAm based estimators of (log transformed) plasma proteins: high sensitivity C-reactive protein (logCRP) and hemoglobin A1C (logA1C). We evaluate GrimAge2 in 13,399 blood samples across nine study cohorts. After adjustment for age and sex, GrimAge2 outperforms GrimAge in predicting mortality across multiple racial/ethnic groups (meta P=3.6x10-167 versus P=2.6x10-144) and in terms of associations with age related conditions such as coronary heart disease, lung function measurement FEV1 (correlation= -0.31, P=1.1x10-136), computed tomography based measurements of fatty liver disease. We present evidence that GrimAge version 2 also applies to younger individuals and to saliva samples where it tracks markers of metabolic syndrome.
DNAm logCRP is positively correlated with morbidity count (P=1.3x10-54). DNAm logA1C is highly associated with type 2 diabetes (P=5.8x10-155). DNAm PAI-1 outperforms the other age-adjusted DNAm biomarkers including GrimAge2 in correlating with triglyceride (cor=0.34, P=9.6x10-267) and visceral fat (cor=0.41, P=4.7x10-41).
Overall, we demonstrate that GrimAge version 2 is an attractive epigenetic biomarker of human mortality and morbidity risk.

Original language	English
Pages (from-to)	9484—9549
Journal	Aging
Volume	14
Issue number	23
Early online date	14 Dec 2022
DOIs	https://doi.org/10.18632/aging.204434
Publication status	E-pub ahead of print - 14 Dec 2022

Keywords / Materials (for Non-textual outputs)

DNA methylation
epigenetic clock
healthspan
mortality

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10.18632/aging.204434Licence: Creative Commons: Attribution (CC-BY)

LuEtaLAU2022DNAMethylationFinal published version, 12.7 MBLicence: Creative Commons: Attribution (CC-BY)

1 Active
3 Finished

Factors of biological ageing: does it all go together when it goes?
Cox, S. (Principal Investigator)
UK-based charities
1/05/21 → 30/04/26
Project: Research
The Lothian Birth Cohort 1936 Waves 6 and 7
Cox, S. (Principal Investigator), Bastin, M. (Co-investigator), Munoz Maniega, S. (Co-investigator), Shenkin, S. (Co-investigator) & Wardlaw, J. (Co-investigator)
Biotechnology and Biological Sciences Research Council
1/04/22 → 31/08/25
Project: Research
Integrated multi-omics prediction of incident Alzheimer's disease and its risk factors
Marioni, R. (Principal Investigator)
UK-based charities
1/09/20 → 31/08/23
Project: Research

Cite this

Lu, A. T., Binder, A. M., Zhang, J., Yan, Q., Reiner, A. P., Cox, S. R., Corley, J., Harris, S., Kuo, P.-L., Moore, A. Z., Bandinelli, S., Stewart, J., Wang, C., Hamlat, E. J., Epel, E. S., Schwartz, J., Whitsel, E. A., Correa, A., Ferrucci, L., ... Horvath, S. (2022). DNA methylation GrimAge version 2. Aging, 14(23), 9484—9549. Advance online publication. https://doi.org/10.18632/aging.204434

@article{f5070dfad6484b5f8da25568610ff822,

title = "DNA methylation GrimAge version 2",

abstract = "We previously described a DNA methylation (DNAm) based biomarker of human mortality risk DNAm GrimAge. Here we describe version 2 of GrimAge (trained on individuals aged between 40 and 92) which leverages two new DNAm based estimators of (log transformed) plasma proteins: high sensitivity C-reactive protein (logCRP) and hemoglobin A1C (logA1C). We evaluate GrimAge2 in 13,399 blood samples across nine study cohorts. After adjustment for age and sex, GrimAge2 outperforms GrimAge in predicting mortality across multiple racial/ethnic groups (meta P=3.6x10-167 versus P=2.6x10-144) and in terms of associations with age related conditions such as coronary heart disease, lung function measurement FEV1 (correlation= -0.31, P=1.1x10-136), computed tomography based measurements of fatty liver disease. We present evidence that GrimAge version 2 also applies to younger individuals and to saliva samples where it tracks markers of metabolic syndrome. DNAm logCRP is positively correlated with morbidity count (P=1.3x10-54). DNAm logA1C is highly associated with type 2 diabetes (P=5.8x10-155). DNAm PAI-1 outperforms the other age-adjusted DNAm biomarkers including GrimAge2 in correlating with triglyceride (cor=0.34, P=9.6x10-267) and visceral fat (cor=0.41, P=4.7x10-41). Overall, we demonstrate that GrimAge version 2 is an attractive epigenetic biomarker of human mortality and morbidity risk.",

keywords = "DNA methylation, epigenetic clock, healthspan, mortality",

author = "Lu, \{Ake T\} and Binder, \{Alexandra M.\} and Joshua Zhang and Qi Yan and Reiner, \{Alex P\} and Cox, \{Simon R.\} and Janie Corley and Sarah Harris and Pei-Lun Kuo and Moore, \{Ann Zenobia\} and Stefania Bandinelli and James Stewart and Cuicui Wang and Hamlat, \{Elissa J\} and Epel, \{Elissa S.\} and Joel Schwartz and Whitsel, \{Eric A\} and Adolfo Correa and Luigi Ferrucci and Marioni, \{Riccardo E\} and Steve Horvath",

year = "2022",

month = dec,

day = "14",

doi = "10.18632/aging.204434",

language = "English",

volume = "14",

pages = "9484—9549",

journal = "Aging",

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T1 - DNA methylation GrimAge version 2

AU - Lu, Ake T

AU - Binder, Alexandra M.

AU - Zhang, Joshua

AU - Yan, Qi

AU - Reiner, Alex P

AU - Cox, Simon R.

AU - Corley, Janie

AU - Harris, Sarah

AU - Kuo, Pei-Lun

AU - Moore, Ann Zenobia

AU - Bandinelli, Stefania

AU - Stewart, James

AU - Wang, Cuicui

AU - Hamlat, Elissa J

AU - Epel, Elissa S.

AU - Schwartz, Joel

AU - Whitsel, Eric A

AU - Correa, Adolfo

AU - Ferrucci, Luigi

AU - Marioni, Riccardo E

AU - Horvath, Steve

PY - 2022/12/14

Y1 - 2022/12/14

N2 - We previously described a DNA methylation (DNAm) based biomarker of human mortality risk DNAm GrimAge. Here we describe version 2 of GrimAge (trained on individuals aged between 40 and 92) which leverages two new DNAm based estimators of (log transformed) plasma proteins: high sensitivity C-reactive protein (logCRP) and hemoglobin A1C (logA1C). We evaluate GrimAge2 in 13,399 blood samples across nine study cohorts. After adjustment for age and sex, GrimAge2 outperforms GrimAge in predicting mortality across multiple racial/ethnic groups (meta P=3.6x10-167 versus P=2.6x10-144) and in terms of associations with age related conditions such as coronary heart disease, lung function measurement FEV1 (correlation= -0.31, P=1.1x10-136), computed tomography based measurements of fatty liver disease. We present evidence that GrimAge version 2 also applies to younger individuals and to saliva samples where it tracks markers of metabolic syndrome. DNAm logCRP is positively correlated with morbidity count (P=1.3x10-54). DNAm logA1C is highly associated with type 2 diabetes (P=5.8x10-155). DNAm PAI-1 outperforms the other age-adjusted DNAm biomarkers including GrimAge2 in correlating with triglyceride (cor=0.34, P=9.6x10-267) and visceral fat (cor=0.41, P=4.7x10-41). Overall, we demonstrate that GrimAge version 2 is an attractive epigenetic biomarker of human mortality and morbidity risk.

AB - We previously described a DNA methylation (DNAm) based biomarker of human mortality risk DNAm GrimAge. Here we describe version 2 of GrimAge (trained on individuals aged between 40 and 92) which leverages two new DNAm based estimators of (log transformed) plasma proteins: high sensitivity C-reactive protein (logCRP) and hemoglobin A1C (logA1C). We evaluate GrimAge2 in 13,399 blood samples across nine study cohorts. After adjustment for age and sex, GrimAge2 outperforms GrimAge in predicting mortality across multiple racial/ethnic groups (meta P=3.6x10-167 versus P=2.6x10-144) and in terms of associations with age related conditions such as coronary heart disease, lung function measurement FEV1 (correlation= -0.31, P=1.1x10-136), computed tomography based measurements of fatty liver disease. We present evidence that GrimAge version 2 also applies to younger individuals and to saliva samples where it tracks markers of metabolic syndrome. DNAm logCRP is positively correlated with morbidity count (P=1.3x10-54). DNAm logA1C is highly associated with type 2 diabetes (P=5.8x10-155). DNAm PAI-1 outperforms the other age-adjusted DNAm biomarkers including GrimAge2 in correlating with triglyceride (cor=0.34, P=9.6x10-267) and visceral fat (cor=0.41, P=4.7x10-41). Overall, we demonstrate that GrimAge version 2 is an attractive epigenetic biomarker of human mortality and morbidity risk.

KW - DNA methylation

KW - epigenetic clock

KW - healthspan

KW - mortality

U2 - 10.18632/aging.204434

DO - 10.18632/aging.204434

M3 - Article

C2 - 36516495

SN - 1945-4589

VL - 14

SP - 9484—9549

JO - Aging

JF - Aging

IS - 23

ER -

DNA methylation GrimAge version 2

Abstract

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Projects

Factors of biological ageing: does it all go together when it goes?

The Lothian Birth Cohort 1936 Waves 6 and 7

Integrated multi-omics prediction of incident Alzheimer's disease and its risk factors

Cite this