Innovative Analytical Methods for DNA Methylation Age

DNA 甲基化时代的创新分析方法

• 批准号: 10414080
• 负责人: Lei Liu
• 金额: $ 23.68万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-01 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10414080
• 关键词: Age; Aging; Biological; Biological Aging; Biological Assay; Biological Markers; Biological Process; Blood; Cardiovascular Diseases; Chronic Disease; Chronology; Clinical; Computer software; Coronary Artery Risk Development in Young Adults Study; DNA Methylation; Data; Development; Disease; Economic Burden; Environmental Risk Factor; Epigenetic Process; Ethnic Origin; Genetic Risk; Grant; Health Surveys; Healthcare Systems; Human; Incidence; Intervention; Joints; Lead; Life; Life Style; Longitudinal Studies; Longitudinal cohort study; Malignant Neoplasms; Measures; Methodology; Methods; Modeling; Modification; Multi-Ethnic Study of Atherosclerosis; Nutrition Surveys; Older Population; Performance; Pharmacologic Substance; Population; Process; Public Health; Research; Research Personnel; Risk; Risk Factors; age related; analytical method; base; biological systems; biomarker identification; cardiovascular health; clinical diagnostics; cohort; cost effectiveness; diagnostic tool; epigenetic marker; epigenome; healthy aging; high dimensionality; improved; indexing; innovation; insight; methylation biomarker; minimally invasive; mortality; racial difference; sample collection; social; success; tool; user-friendly

Project Summary/Abstract As the US population continues to age in the coming years, the need for biological measures and biomarkers of aging becomes increasingly urgent. Finding and validating biomarkers of aging continues to attract research efforts, but with limited success. Epigenetic modifications are potentially critical to the biological processes that underlie aging (Ben-Avraham et al. 2012). More recently, DNA methylation levels (DNAm) have been identified as useful tools for defining biological age, as Hannum et al. (2013) and Horvath (2013) both combined DNAm at multiple loci to quantify human aging. This “DNA methylation age” predicted all-cause mortality later in life (Marioni et al. 2015). Both Hannum and Horvath applied the ultra-high dimensional (~485K DNA methylation markers) variable selection methodology with elastic net penalty (Zou and Hastie 2005) to derive their epigenetic age indices. However, there are several issues in the original approaches by these researchers. In this grant, we propose more accurate and robust epigenetic age models using ultra-high dimensional DNA methylation markers. We also consider longitudinal DNAm data. We will develop and disseminate a user-friendly statistical software package that will enable researchers to implement these methods with ease. We will apply our methods to two large longitudinal cohort studies: the Coronary Artery Risk Development in Young Adults (CARDIA) and Multi- Ethnic Study of Atherosclerosis (MESA). Our discoveries may illustrate the biological mechanisms underlying traditional and innovative risk factors for mortality and discover more accurate and reliable markers for biological aging. Potential clinical, lifestyle, and pharmaceutical interventions can thus be developed for healthy aging.

项目总结/文摘