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

Li, Xiangwei ; Delerue, Thomas; Schöttker, Ben; Holleczek, Bernd; Grill, Eva ; Peters, Annette ; Waldenberger, Melanie ; Thorand, Barbara ; Brenner, Hermann (2022): Derivation and validation of an epigenetic frailty risk score in population-based cohorts of older adults. In: Nature Communications, Vol. 13, 5269

Abstract

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.

• Item Type: Journal article
• Faculties: Medicine > Institute for Medical Information Processing, Biometry and Epidemiology; Medicine > Institute for Medical Information Processing, Biometry and Epidemiology > Epidemiology of Vertigo and Dizziness
• Subjects: 600 Technology > 610 Medicine and health
• ISSN: 2041-1723
• Language: English