Dataset Information

Methylomic survival predictors, frailty, and mortality.

ABSTRACT: Survival predictors are of potential use for informing on biological age and targeting prevention of aging-related morbidity. We assessed associations of 2 novel methylomic survival indicators, a methylation-based mortality risk score (MRscore) and the epigenetic clock-derived age acceleration (AA), with a well-known survival predictor, frailty index (FI), and compared the 3 indicators in mortality prediction. In a large population-based cohort with 14-year follow-up, we found both MRscore and AA to be independently associated with FI, but the association was much stronger for MRscore than for AA. Although all 3 indicators were individually associated with all-cause mortality, robust associations only persisted for MRscore and FI when simultaneously including the 3 indicators in regression models, with hazard ratios (95% CI) of 1.91 (1.63-2.22), 1.37 (1.25-1.51), and 1.05 (0.90-1.22), respectively, per standard deviation increase of MRscore, FI, and AA. Prediction error curves, Harrell's C-statistics, and time-dependent AUCs all showed higher predictive accuracy for MRscore than for FI and AA. These findings were validated in independent samples. Our study demonstrates the ability of the MRscore to strongly enhance survival prediction beyond established markers of biological age, such as FI and AA, and it thus bears potential of a surrogate endpoint for clinical research and intervention.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC5892685 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Methylomic survival predictors, frailty, and mortality.

Zhang Yan Y Saum Kai-Uwe KU Schöttker Ben B Holleczek Bernd B Brenner Hermann H

Aging 20180301 3

Survival predictors are of potential use for informing on biological age and targeting prevention of aging-related morbidity. We assessed associations of 2 novel methylomic survival indicators, a methylation-based mortality risk score (MRscore) and the epigenetic clock-derived age acceleration (AA), with a well-known survival predictor, frailty index (FI), and compared the 3 indicators in mortality prediction. In a large population-based cohort with 14-year follow-up, we found both MRscore and A ...[more]

PMID: 29514134

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Project description:BackgroundSocial vulnerability is related to the health of elderly people, but its measurement and relationship to frailty are controversial. The aims of the present study were to operationalize social vulnerability according to a deficit accumulation approach, to compare social vulnerability and frailty, and to study social vulnerability in relation to mortality.Methods and findingsThis is a secondary analysis of community-dwelling elderly people in two cohort studies, the Canadian Study of Health and Aging (CSHA, 1996/7-2001/2; N = 3707) and the National Population Health Survey (NPHS, 1994-2002; N = 2648). Social vulnerability index measures that used self-reported items (23 in NPHS, 40 in CSHA) were constructed. Each measure ranges from 0 (no vulnerability) to 1 (maximum vulnerability). The primary outcome measure was mortality over five (CHSA) or eight (NPHS) years. Associations with age, sex, and frailty (as measured by an analogously constructed frailty index) were also studied. All individuals had some degree of social vulnerability. Women had higher social vulnerability than men, and vulnerability increased with age. Frailty and social vulnerability were moderately correlated. Adjusting for age, sex, and frailty, each additional social 'deficit' was associated with an increased odds of mortality (5 years in CSHA, odds ratio = 1.05, 95% confidence interval: 1.02-1.07; 8 years in the NPHS, odds ratio = 1.08, 95% confidence interval: 1.03-1.14). We identified a meaningful survival gradient across quartiles of social vulnerability, and although women had better survival than men, survival for women with high social vulnerability was equivalent to that of men with low vulnerability.ConclusionsSocial vulnerability is reproducibly related to individual frailty/fitness, but distinct from it. Greater social vulnerability is associated with mortality in older adults. Further study on the measurement and operationalization of social vulnerability, and of its relationships to other important health outcomes, is warranted.

Dataset Information

Methylomic survival predictors, frailty, and mortality.

Publications

Methylomic survival predictors, frailty, and mortality.

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