DNA methylation-based biomarkers of age acceleration and all-cause death, myocardial infarction, stroke, and cancer in two cohorts: The NAS, and KORA F4

Wang, Cuicui; Ni, Wenli; Yao, Yueli; Just, Allan C.; Heiss, Jonathan; Wei, Yaguang; Gao, Xu; Coull, Brent A.; Kosheleva, Anna; Baccarelli, Andrea A.; Peters, Annette; Schwartz, Joel

doi:10.1016/j.ebiom.2020.103151

Cited by 44 publications

(33 citation statements)

References 70 publications

(100 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our findings are in line with the literature in cohorts of European ancestry, showing that GrimAA outperforms other measures in its association with CVD incidence [ 21 , 22 ]. The effect size of GrimAA on CVD incidence appears to be remarkably similar across studies in European ancestry, and similar to our estimate in African Americans.…”

Section: Discussionsupporting

confidence: 92%

“…Comparing the same four measures of epigenetic acceleration that we investigated, Hillary et al found that over thirteen years of follow-up, GrimAA outperforms the other measures in terms of its association with incidence of heart disease (HR: 1.41, 95% CI 1.18–1.68, per 1 SD) [ 21 ]. Wang et al found that a 1 SD increase in GrimAA was associated with elevated risk of myocardial infarction (HR: 1.44, 95% CI 1.16–1.79) and stroke (HR: 1.42, 95% CI 1.06–1.91) in a study of elderly participants from the Normative Ageing Study and the Cooperative Health Research in the Region of Augsburg (KORA) study [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

“…PhenoAge and GrimAge are more recently developed measures, and so validation of their associations and comparisons to the first-generation measures are in early stages. Two recent studies in participants of European ancestry show that GrimAA outperforms other measures in its association with CVD incidence after adjusting for CVD risk factors [ 21 , 22 ], and additional studies report similar findings with all-cause mortality [ 21 – 24 ]. Yet it is unclear whether epigenetic age acceleration measures could be used to improve CVD prediction in a clinical setting.…”

Section: Introductionmentioning

confidence: 93%

See 2 more Smart Citations

Epigenetic age acceleration is associated with cardiometabolic risk factors and clinical cardiovascular disease risk scores in African Americans

et al. 2021

View full text Add to dashboard Cite

Background Cardiovascular disease (CVD) is the leading cause of mortality among US adults. African Americans have higher burden of CVD morbidity and mortality compared to any other racial group. Identifying biomarkers for clinical risk prediction of CVD offers an opportunity for precision prevention and earlier intervention. Results Using linear mixed models, we investigated the cross-sectional association between four measures of epigenetic age acceleration (intrinsic (IEAA), extrinsic (EEAA), PhenoAge (PhenoAA), and GrimAge (GrimAA)) and ten cardiometabolic markers of hypertension, insulin resistance, and dyslipidemia in 1,100 primarily hypertensive African Americans from sibships in the Genetic Epidemiology Network of Arteriopathy (GENOA). We then assessed the association between epigenetic age acceleration and time to self-reported incident CVD using frailty hazard models and investigated CVD risk prediction improvement compared to models with clinical risk scores (Framingham risk score (FRS) and the atherosclerotic cardiovascular disease (ASCVD) risk equation). After adjusting for sex and chronological age, increased epigenetic age acceleration was associated with higher systolic blood pressure (IEAA), higher pulse pressure (EEAA and GrimAA), higher fasting glucose (PhenoAA and GrimAA), higher fasting insulin (EEAA), lower low density cholesterol (GrimAA), and higher triglycerides (GrimAA). A five-year increase in GrimAA was associated with CVD incidence with a hazard ratio of 1.54 (95% CI 1.22–2.01) and remained significant after adjusting for CVD risk factors. The addition of GrimAA to risk score models improved model fit using likelihood ratio tests (P = 0.013 for FRS and P = 0.008 for ASCVD), but did not improve C statistics (P > 0.05). Net reclassification index (NRI) showed small but significant improvement in reassignment of risk categories with the addition of GrimAA to FRS (NRI: 0.055, 95% CI 0.040–0.071) and the ASCVD equation (NRI: 0.029, 95% CI 0.006–0.064). Conclusions Epigenetic age acceleration measures are associated with traditional CVD risk factors in an African-American cohort with a high prevalence of hypertension. GrimAA was associated with CVD incidence and slightly improved prediction of CVD events over clinical risk scores.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 93%

See 1 more Smart Citation

Epigenetic age acceleration is associated with cardiometabolic risk factors and clinical cardiovascular disease risk scores in African Americans

et al. 2021

View full text Add to dashboard Cite

show abstract

“…2019 ). Similarly, a longitudinal analysis of data from two cohorts of older individuals (

, mean follow-up of

) reported that, of the four DNAmAgeAC metrics assessed, GrimAge acceleration had the strongest and most consistent associations with mortality, myocardial infarction, and stroke ( Wang et al. 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Surrounding Greenness and Biological Aging Based on DNA Methylation: A Twin and Family Study in Australia

et al. 2021

Environ Health Perspect

View full text Add to dashboard Cite

Background: High surrounding greenness has many health benefits and might contribute to slower biological aging. However, very few studies have evaluated this from the perspective of epigenetics. Objectives: We aimed to evaluate the association between surrounding greenness and biological aging based on DNA methylation. Methods: We derived Horvath’s DNA methylation age (DNAmAge), Hannum’s DNAmAge, PhenoAge, and GrimAge based on DNA methylation measured in peripheral blood samples from 479 Australian women in 130 families. Measures of DNAmAge acceleration (DNAmAgeAC) were derived from the residuals after regressing each DNAmAge metric on chronological age. Greenness was represented by satellite-derived Normalized Difference Vegetation Index (NDVI) and Enhanced Vegetation Index (EVI) metrics within 300-, 500-, 1,000-, and buffers surrounding participant addresses. Greenness-DNAmAgeAC associations were estimated using a within-sibship design fitted by linear mixed effect models, adjusting for familial clustering and important covariates. Results: Greenness metrics were associated with significantly lower DNAmAgeAC based on GrimAge acceleration, suggesting slower biological aging with higher greenness based on both NDVI and EVI in buffer areas. For example, each interquartile range increase in NDVI within was associated with a 0.59 (95% CI: 0.18, 1.01)–year decrease in GrimAge acceleration. Greenness was also inversely associated with three of the eight components of GrimAge, specifically, DNA methylation-based surrogates of serum cystatin-C, serum growth differentiation factor 15, and smoking pack years. Associations between greenness and biological aging measured by Horvath’s and Hannum’s DNAmAgeAC were less consistent, and depended on neighborhood socioeconomic status. No significant associations were estimated for PhenoAge acceleration. Discussion: Higher surrounding greenness was associated with slower biological aging, as indicated by GrimAge age acceleration, in Australian women. Associations were also evident for three individual components of GrimAge, but were inconsistent for other measures of biological aging. Additional studies are needed to confirm our results. https://doi.org/10.1289/EHP8793

show abstract

“…Therefore, DNAm age are thought to represent “biological” age. Consistently, DNAmaa has been shown to reliably predict age-related morbidity and mortality [ 7 , 8 , 9 , 10 , 11 ]. Because genome-wide DNA methylation studies show shared epigenomic features between aging and cancer, providing explanations for their possible molecular links [ 12 , 13 , 14 ], the role for DNAm age in carcinogenesis has been recently explored.…”

Section: Introductionmentioning

confidence: 94%

DNA Methylation Age Drift Is Associated with Poor Outcomes and De-Differentiation in Papillary and Follicular Thyroid Carcinomas

Liu

Wang

Xiu

et al. 2021

Cancers

View full text Add to dashboard Cite

Alterations in global DNA methylation play a critical role in both aging and cancer, and DNA methylation (DNAm) age drift has been implicated in cancer risk and pathogenesis. In the present study, we analyzed the TCGA cohort of papillary and follicular thyroid carcinoma (PTC and FTC) for their DNAm age and association with clinic-pathological features. In 54 noncancerous thyroid (NT) samples, DNAm age was highly correlated with patient chronological age (R2 = 0.928, p = 2.6 × 10−31), but drifted to younger than chronological age in most specimens, especially those from patients >50 years old. DNAm age in 502 tumors was also correlated with patient chronological age, but to a much lesser extent (R2 = 0.403). Highly drifted DNAm age (HDDA) was identified in 161 tumors, among which were 101 with DNAm age acceleration while 60 with DNAm age deceleration. Tumors with HDDA were characterized by the robust aberrations in metabolic activities, extracellular microenvironment components and inflammation/immunology responses, and dedifferentiation. Importantly, HDDA in tumors independently predicted shorter disease-free survival of patients. Collectively, NT thyroids from TC patients have younger DNAm age, while HDDA frequently occurs in TCs, and contributes to the TC progression and poor patient outcomes. HDDA may serve as a new prognostic factor for TCs.

show abstract

DNA methylation-based biomarkers of age acceleration and all-cause death, myocardial infarction, stroke, and cancer in two cohorts: The NAS, and KORA F4

Cited by 44 publications

References 70 publications

Epigenetic age acceleration is associated with cardiometabolic risk factors and clinical cardiovascular disease risk scores in African Americans

Epigenetic age acceleration is associated with cardiometabolic risk factors and clinical cardiovascular disease risk scores in African Americans

Surrounding Greenness and Biological Aging Based on DNA Methylation: A Twin and Family Study in Australia

DNA Methylation Age Drift Is Associated with Poor Outcomes and De-Differentiation in Papillary and Follicular Thyroid Carcinomas

Contact Info

Product

Resources

About