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Li, Xiangwei ORCID: 0000-0002-9450-7771; Delerue, Thomas; Schöttker, Ben; Holleczek, Bernd; Grill, Eva ORCID: 0000-0002-0273-7984; Peters, Annette ORCID: 0000-0001-6645-0985; Waldenberger, Melanie ORCID: 0000-0003-0583-5093; Thorand, Barbara ORCID: 0000-0002-8416-6440; Brenner, Hermann ORCID: 0000-0002-6129-1572 (2022): Derivation and validation of an epigenetic frailty risk score in population-based cohorts of older adults. In: Nature Communications, Vol. 13, 5269
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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.