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.

项目摘要/摘要 随着未来几年美国人口的持续年龄，对生物学措施和生物标志物的需求 衰老变得越来越紧迫。寻找和验证衰老的生物标志物继续吸引研究 努力，但成功有限。 表观遗传修饰对于衰老的生物学过程至关重要（Ben-Avraham et al。 2012）。最近，DNA甲基化水平（DNAM）已被确定为定义的有用工具 生物年龄，如Hannum等人。 （2013）和Horvath（2013）均在多个本地合并DNAM来量化 人类衰老。这种“ DNA甲基化年龄”预测了生命后期的全因死亡率（Marioni等，2015）。 Hannum和Horvath都应用了超高维（〜485k DNA甲基化标记）变量 弹性净惩罚的选择方法（Zou and Hastie 2005）得出其表观遗传年龄指数。 但是，这些研究人员的原始方法中有几个问题。在这笔赠款中，我们建议 使用超高尺寸DNA甲基化标记物更准确，更稳固的表观遗传年龄模型。我们 还考虑纵向dnam数据。我们将开发并传播一个用户友好的统计软件 可以使研究人员轻松实施这些方法的软件包。我们将把我们的方法应用于两个 大型纵向队列研究：年轻人（Cardia）和多人的冠状动脉风险发展 动脉粥样硬化的种族研究（MESA）。 我们的发现可能说明传统和创新风险因素的生物学机制 死亡率并发现生物衰老的更准确和可靠的标记。潜在的临床，生活方式和 因此，可以为健康的衰老而开发药物干预措施。