Derivation and validation of an epigenetic frailty risk score in population-based cohorts of older adults

DNA methylation (DNAm) patterns in peripheral blood have been shown to be associated with aging related health outcomes. We perform an epigenome-wide screening to identify CpGs related to frailty, defined by a frailty index (FI), in a large population-based cohort of older adults from Germany, the E...

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Veröffentlicht in:Nature communications Jg. 13; H. 1; S. 5269 - 11
Hauptverfasser: Li, Xiangwei, Delerue, Thomas, Schöttker, Ben, Holleczek, Bernd, Grill, Eva, Peters, Annette, Waldenberger, Melanie, Thorand, Barbara, Brenner, Hermann
Format: Journal Article
Sprache:Englisch
Veröffentlicht: London Nature Publishing Group UK 07.09.2022
Nature Publishing Group
Nature Portfolio
Schlagworte:
631/208/176/1988
692/308/174
692/308/53/2423
692/700/1518
Adults
Aging
Algorithms
Deoxyribonucleic acid
DNA
DNA methylation
Epigenetics
Frailty
Humanities and Social Sciences
multidisciplinary
Older people
Performance prediction
Peripheral blood
Population studies
Risk analysis
Risk factors
Science
Science (multidisciplinary)
Wide screen
ISSN:2041-1723, 2041-1723
Online-Zugang:Volltext
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Zusammenfassung:DNA methylation (DNAm) patterns in peripheral blood have been shown to be associated with aging related health outcomes. We perform an epigenome-wide screening to identify CpGs related to frailty, defined by a frailty index (FI), in a large population-based cohort of older adults from Germany, the ESTHER study. Sixty-five CpGs are identified as frailty related methylation loci. Using LASSO regression, 20 CpGs are selected to derive a DNAm based algorithm for predicting frailty, the epigenetic frailty risk score (eFRS). The eFRS exhibits strong associations with frailty at baseline and after up to five-years of follow-up independently of established frailty risk factors. These associations are confirmed in another independent population-based cohort study, the KORA-Age study, conducted in older adults. In conclusion, we identify 65 CpGs as frailty-related loci, of which 20 CpGs are used to calculate the eFRS with predictive performance for frailty over long-term follow-up. Frailty is associated with an increased risk for negative health outcomes in older populations, and being able to predict frailty could facilitate prevention measures. By performing an epigenome-wide screen, the authors derived a DNA methylation based measure for frailty which can predict both prevalence and longer-term incidence of frailty.
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-022-32893-x