Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120, Heidelberg, Germany.
Medical Faculty Heidelberg, University of Heidelberg, Im Neuenheimer Feld 672, 69120, Heidelberg, Germany.
Nat Commun. 2022 Sep 7;13(1):5269. doi: 10.1038/s41467-022-32893-x.
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.
外周血中的 DNA 甲基化 (DNAm) 模式已被证明与衰老相关的健康结果有关。我们在一个来自德国的大型基于人群的老年人队列中进行了全基因组范围的筛查，以确定与脆弱性相关的 CpG，脆弱性由虚弱指数 (FI) 定义。65 个 CpG 被确定为与脆弱性相关的甲基化位点。使用 LASSO 回归，选择 20 个 CpG 来推导基于 DNAm 的算法，用于预测脆弱性，即表观遗传脆弱性风险评分 (eFRS)。eFRS 与基线时的脆弱性以及在长达五年的随访后独立于既定的脆弱性危险因素具有很强的关联。这些关联在另一个独立的基于人群的队列研究，即 KORA-Age 研究中，在老年人中得到了证实。总之，我们确定了 65 个与脆弱性相关的 CpG 作为脆弱性相关的位点，其中 20 个 CpG 用于计算 eFRS，该评分具有对长期随访中脆弱性的预测性能。
