DNA methylation biomarker in blood predicts frailty in an HIV-positive veteran population

Autor: Shu, Chang, Justice, Amy C., Zhang, Xinyu, Marconi, Vincent C., Hancock, Dana B., Johnson, Eric O., Xu, Ke
Jazyk: angličtina
Rok vydání: 2019
DOI: 10.1101/19010272
Popis: Background: With the improved life expectancy in people living with HIV, predicting individual frailty is important for clinical care. DNA methylation (DNAm) has emerged as a robust biomarker in precision medicine and has been previously linked to aging and mortality in non-HIV populations. Here, we aim to establish a panel of DNAm features selected from blood methylome to predict frailty in HIV-positive men from a veteran population, Veterans Aging Cohort Study (VACS). Methods: We used a well-established score, VACS Index, as a measure of frailty. Samples (ntotal=1,150) were divided into a training set (n=612) and a validation set (n=538). We first selected a panel of frailty-associated CpGs by conducting an epigenome-wide association analysis on the VACS index in the training set. We then applied four machine learning methods to build models to predict high and low frailty individuals in the training set. The prediction models were tested in the validation set. A methylation score constructed from the selected CpGs was tested an associated with mortality by performing survival analysis. To assess the biological relevance of the selected CpG sites, we performed a gene ontology enrichment analysis. Results: A panel of 119 CpGs were identified from the training set (False Discovery Rate
Databáze: OpenAIRE