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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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Main Authors: Li, Xiangwei (Author) , Delerue, Thomas (Author) , Schöttker, Ben (Author) , Holleczek, Bernd (Author) , Grill, Eva (Author) , Peters, Annette (Author) , Waldenberger, Melanie (Author) , Thorand, Barbara (Author) , Brenner, Hermann (Author)
Format: Article (Journal)
Language:English
Published: 07 September 2022
In: Nature Communications
Year: 2022, Volume: 13, Pages: 1-11
ISSN:2041-1723
DOI:10.1038/s41467-022-32893-x
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/s41467-022-32893-x
Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/s41467-022-32893-x
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Author Notes:Xiangwei Li, Thomas Delerue, Ben Schöttker, Bernd Holleczek, Eva Grill, Annette Peters, Melanie Waldenberger, Barbara Thorand & Hermann Brenner
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Summary: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 Description:Gesehen am 02.11.2022
Physical Description:Online Resource
ISSN:2041-1723
DOI:10.1038/s41467-022-32893-x

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