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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Detalles Bibliográficos
Autores principales: Li, Xiangwei, Delerue, Thomas, Schöttker, Ben, Holleczek, Bernd, Grill, Eva, Peters, Annette, Waldenberger, Melanie, Thorand, Barbara, Brenner, Hermann
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9450828/
https://www.ncbi.nlm.nih.gov/pubmed/36071044
http://dx.doi.org/10.1038/s41467-022-32893-x
Descripción
Sumario: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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