Methylomic survival predictors, frailty, and mortality

Zhang, Yan; Saum, Kai Uwe; Schöttker, Ben; Holleczek, Bernd; Brenner, Hermann

doi:10.18632/aging.101392

Cited by 27 publications

(25 citation statements)

References 42 publications

(52 reference statements)

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“…The main analyses were conducted with the ESTHER longitudinal cohort initiated in 2000–2002 (baseline) in the German state of Saarland and including in total 9940 participants aged 50–75 years 10 . Part of the analyses were replicated in the independent KORA F4 study, which was initiated in 2006–2008 in the German region of Augsburg and included 3,080 participants aged 32–81 years 11 – 13 .…”

Section: Methodsmentioning

confidence: 99%

Subjective mental health, incidence of depressive symptoms in later life, and the role of epigenetics: results from two longitudinal cohort studies

et al. 2020

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The role of self-perceived general health in predicting morbidity and mortality among older people is established. The predictive value of self-perceived mental health and of its possible biological underpinnings for future depressive symptoms is unexplored. This study aimed to assess the role of mental health-related quality of life (HRQOL) and of its epigenetic markers in predicting depressive symptoms among older people without lifetime history of depression. Data were based on a subgroup (n = 1 492) of participants of the longitudinal ESTHER study. An epigenome-wide association study (EWAS) of mental HRQOL was conducted using DNA from baseline whole blood samples and logistic regression analyses were performed to assess the predictive value of methylation beta values of EWAS identified CpGs for incidence of depressive symptoms in later life. The methylation analyses were replicated in the independent KORA cohort (n = 890) and a meta-analysis of the two studies was conducted. Results of the meta-analysis showed that participants with beta values of cg27115863 within quartile 1 (Q1) had nearly a two-fold increased risk of developing depressive symptoms compared to participants with beta values within Q4 (ORQ1vsQ4 = 1.80; CI 1.25–2.61). In the ESTHER study the predictive value of subjective mental health for future depressive symptoms was also assessed and for 10-unit increase in mental HRQOL scores the odds for incident depressive symptoms were reduced by 54% (OR 0.46; CI 0.40–0.54). These findings suggest that subjective mental health and hypomethylation at cg27115863 are predictive of depressive symptoms, possibly through the activation of inflammatory signaling pathway.

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Section: Methodsmentioning

confidence: 99%

Subjective mental health, incidence of depressive symptoms in later life, and the role of epigenetics: results from two longitudinal cohort studies

et al. 2020

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“…In their study, they independently validated the strong association of DNAmRS and mortality among 1700 subjects in cooperative health research in the region of augsburg cohort (KORA F4) [23] . DNAmRS is a linear combination of 10 probes selected by least absolute shrinkage and selection operator (LASSO) regression and has been reported as a strong predictor for all-cause, and cardiovascular mortality [ 23 , 24 ] Recently, our group found that DNAmRS was more predictive for all-cause, cardiovascular, and cancer mortality compared with telomere length, and PhenoAgeAccel [25] . However, when we conducted this analysis, GrimAgeAccel had not been generated yet; neither IEAA, nor EEAA were examined.…”

Section: Introductionmentioning

confidence: 99%

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

Ni²,

Yao³

et al. 2021

EBioMedicine

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“…Are other recently developed EA indices that use methylation arrays also subject to ethnic specific genetic effects? The Brenner Frailty index bases its prediction on the information from a relative handful (34) of CpG sites [ 47 ]. If the amount of confounding is proportional to the number of probes, then the effects on this index are likely less severe.…”

Section: Discussionmentioning

confidence: 99%

Array-Based Epigenetic Aging Indices May Be Racially Biased

Philibert

Beach

Simons

et al. 2020

Genes

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Epigenetic aging (EA) indices are frequently used as predictors of mortality and other important health outcomes. However, each of the commonly used array-based indices has significant heritable components which could tag ethnicity and potentially confound comparisons across racial and ethnic groups. To determine if this was possible, we examined the relationship of DNA methylation in cord blood from 203 newborns (112 African American (AA) and 91 White) at the 513 probes from the Levine PhenoAge Epigenetic Aging index to ethnicity. Then, we examined all sites significantly associated with race in the newborn sample to determine if they were also associated with an index of ethnic genetic heritage in a cohort of 505 AA adults. After Bonferroni correction, methylation at 50 CpG sites was significantly associated with ethnicity in the newborn cohort. The five most significant sites predicted ancestry with a receiver operator characteristic area under the curve of 0.97. Examination of the top 50 sites in the AA adult cohort showed that methylation status at 11 of those sites was also associated with percentage European ancestry. We conclude that the Levine PhenoAge Index is influenced by cryptic ethnic-specific genetic influences. This influence may extend to similarly constructed EA indices and bias cross-race comparisons.

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Methylomic survival predictors, frailty, and mortality

Cited by 27 publications

References 42 publications

Subjective mental health, incidence of depressive symptoms in later life, and the role of epigenetics: results from two longitudinal cohort studies

Subjective mental health, incidence of depressive symptoms in later life, and the role of epigenetics: results from two longitudinal cohort studies

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

Array-Based Epigenetic Aging Indices May Be Racially Biased

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