Integrated Personalized Epigenome Profiling and the Effect of Dietary Exposure on Individuals at Risk for Type-2-Diabetes

综合个性化表观基因组分析以及饮食暴露对 2 型糖尿病风险个体的影响

• 批准号: 9170234
• 负责人: Kevin Van Bortle
• 金额: $ 5.43万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-28 至 2018-09-27
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9170234
• 关键词: ATAC-seq; Accounting; Binding; Biological Assay; Biological Markers; Blood specimen; Body Weight decreased; Cardiovascular Diseases; Cell Count; Cell physiology; Chromatin; Complex; DNA Methylation; DNA mapping; Data; Deoxyribonucleases; Diabetes Mellitus; Diet; Disease; Disease susceptibility; Enrollment; Environmental Exposure; Environmental Risk Factor; Epidemiologic Studies; Epigenetic Process; Formaldehyde; Gene Expression; Genes; Genetic; Genome; Genomic approach; Health; Human; Individual; Insulin; Insulin Resistance; Laboratories; Learning; Life Style; Malignant Neoplasms; Maps; Measurable; Methods; Molecular; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Pathogenesis; Pathway interactions; Patients; Peripheral Blood Mononuclear Cell; Physiology; Population; Proteins; Proteome; Proteomics; Regulatory Element; Risk; Role; Sampling; Shapes; Short-Term Course; Susceptibility Gene; Time; Transcript; Transposase; Virus Diseases; Weight Gain; cell type; clinically relevant; cohort; diabetic patient; disorder risk; epigenetic profiling; epigenome; gene environment interaction; genome-wide; high risk; human subject; improved; insight; insulin secretion; metabolome; metabolomics; methylation pattern; microbiome; non-diabetic; novel; nutrition; patient oriented; personalized medicine; potential biomarker; prevent; public health relevance; response; transcription factor; transcriptome; transcriptomics

 DESCRIPTION (provided by applicant): Disease risk is governed by complex interactions between an individual's genetic background and environmental exposures, yet very little is currently understood about how environmental factors influence the genome. Recent studies suggest that dietary exposure, a key environmental factor with roles in the pathogenesis of obesity, type-2-diabetes (T2D), and other complex diseases, modulates gene expression through epigenetic mechanisms. It is therefore likely that the epigenome, defined here as the overall epigenetic profile of an individual in a given cell type, represents a dynamic, reprogrammable interface through which dietary exposure shapes cellular function and disease susceptibility. Here we propose to comprehensively characterize the epigenome in individuals at high- and low-risk for developing T2D during the course of short- term overfeeding. Personalized epigenome profiles will be generated by mapping both chromatin accessibility and DNA methylation patterns in peripheral blood mononuclear cells, and integrated with transcriptomic, proteomic, and metabolomic analyses. This proposal represents the first personalized, integrative epigenome mapping study of its kind. We hypothesize that changes in diet will correlate with measurable, dynamic epigenetic signatures, which will provide important insight into the mechanisms underlying gene-environment interactions and yield clinically-relevant biomarkers for both exposure and disease.

 疾病风险受个体遗传背景和环境暴露之间复杂相互作用的影响，但目前对环境因素如何影响基因组知之甚少。最近的研究表明，饮食暴露，一个关键的环境因素，在肥胖症，2型糖尿病（T2 D）和其他复杂疾病的发病机制中的作用，通过表观遗传机制调节基因表达。因此，表观基因组（此处定义为给定细胞类型中个体的总体表观遗传特征）可能代表了一个动态的、可重新编程的界面，通过该界面，饮食暴露塑造了细胞功能和疾病易感性。在这里，我们建议全面表征在短期过度喂养过程中发展T2 D的高风险和低风险个体的表观基因组。将通过绘制外周血单核细胞中的染色质可及性和DNA甲基化模式来生成个性化表观基因组图谱，并与转录组学、蛋白质组学和代谢组学分析相结合。这一提议代表了同类研究中第一个个性化的、综合性的表观基因组作图研究。我们假设饮食的变化将与可测量的、动态的表观遗传特征相关，这将为了解基因-环境相互作用的机制提供重要的见解，并为暴露和疾病提供临床相关的生物标志物。