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Li, X.* ; Delerue, T. ; Schöttker, B.* ; Holleczek, B.* ; Grill, E.* ; Peters, A. ; Waldenberger, M. ; Thorand, B.* ; Brenner, H.*

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

Nat. Commun. 13:5269 (2022)

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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.

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