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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.

SUBMITTER: Lu AT

PROVIDER: S-EPMC9792204 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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DNA methylation GrimAge version 2.

Lu Ake T AT Binder Alexandra M AM Zhang Joshua J Yan Qi Q Reiner Alex P AP Cox Simon R SR Corley Janie J Harris Sarah E SE Kuo Pei-Lun PL Moore Ann Z AZ Bandinelli Stefania S Stewart James D JD Wang Cuicui C Hamlat Elissa J EJ Epel Elissa S ES Schwartz Joel D JD Whitsel Eric A EA Correa Adolfo A Ferrucci Luigi L Marioni Riccardo E RE Horvath Steve S

Aging 20221214 23

We previously described a DNA methylation (DNAm) based biomarker of human mortality risk <i>DNAm GrimAge</i>. 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 predicti ...[more]

PMID: 36516495

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Project description:Background: Cumulative exposure to violence can change the regulation of epigenetic and physiological markers. Although violence has been associated with accelerated cellular aging, little is known about associations with cardiac autonomic activity.Objective: The current study aimed to investigate the relationship of exposure to community and domestic violence (CDV) with vagal activity and epigenetic aging acceleration.Methods: A total of 86 adolescents (57% female) were evaluated and interviewed at two time-points in São Gonçalo (2014-2019), a Brazilian city with high levels of violence. Exposure to CDV was assessed in both time-points. GrimAge acceleration was calculated from saliva DNA methylation using Infinium HumanMethylation450K (Illumina) collected in the first assessment. Heart rate variability (HRV) was collected during two stress tasks at the second assessment.Results: The exposure to violence witnessed or directly experienced at home and in the community increased significantly (t = 4.87, p < .01) across two-time points, and males had reported higher violence exposure (t = 2.06, p = .043). Violence at 1st assessment was significantly associated with GrimAge acceleration (B = .039, p value = .043). Violence at both assessments were associated with HRV measured during the narration of the worst trauma (traumaHRV) (B = .009, p value = .039, and B = .007, p value = .024, 1st and 2nd assessment respectively). GrimAge acceleration was significantly associated with traumaHRV (B = .043, p value = .049), and HRV measured during a 3D roller coaster video (B = .061, p value = .024).Conclusions: We found relevant evidence that experiencing violence during adolescence is associated with epigenetic aging and stress-related vagal activity. Understanding these factors during this period could contribute to the development of early interventions for health promotion.HIGHLIGHTS Higher exposure to Community and domestic violence is associated with increased GrimAge acceleration.Higher GrimAge acceleration is associated with increased stress-related vagal activity.Exposure to community and domestic violence increased significantly over time.

Dataset Information

DNA methylation GrimAge version 2.

Publications

DNA methylation GrimAge version 2.

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