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

被引：0
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作者：
Xiangwei Li
Thomas Delerue
Ben Schöttker
Bernd Holleczek
Eva Grill
Annette Peters
Melanie Waldenberger
Barbara Thorand
Hermann Brenner
机构：
[1] German Cancer Research Center (DKFZ),Division of Clinical Epidemiology and Aging Research
[2] University of Heidelberg,Medical Faculty Heidelberg
[3] German Research Center for Environmental Health,Research Unit Molecular Epidemiology, Institute of Epidemiology, Helmholtz Zentrum München
[4] University of Heidelberg,Network Aging Research
[5] Krebsregister Saarland,Saarland Cancer Registry
[6] Ludwig-Maximilians-Universität München,Institute for Medical Information Processing, Biometry and Epidemiology
[7] Klinikum der Universität München,German Center for Vertigo and Balance Disorders
[8] German Research Center for Environmental Health,Institute of Epidemiology, Helmholtz Zentrum München
[9] Ludwig-Maximilians-Universität München,Institute for Medical Informatics, Biometrics and Epidemiology
[10] Partner Site Munich Heart Alliance,German Center for Cardiovascular Research (DZHK)
[11] German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT),Division of Preventive Oncology
[12] German Cancer Research Center (DKFZ),German Cancer Consortium
来源：
Nature Communications | / 13卷
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摘要：
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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