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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Vydané v:Nature communications Ročník 13; číslo 1; s. 5269 - 11
Hlavní autori: Li, Xiangwei, Delerue, Thomas, Schöttker, Ben, Holleczek, Bernd, Grill, Eva, Peters, Annette, Waldenberger, Melanie, Thorand, Barbara, Brenner, Hermann
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: London Nature Publishing Group UK 07.09.2022
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ISSN:2041-1723, 2041-1723
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Shrnutí: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