Foundational studies for precision nutrition

精准营养的基础研究

• 批准号: 10410563
• 负责人: DAVID W. THREADGILL
• 金额: $ 65.3万
• 依托单位: TEXAS A&M AGRILIFE RESEARCH
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10410563
• 关键词: Address; American; Behavior; Behavior Therapy; Biological; Biological Markers; Cardiometabolic Disease; Characteristics; Communities; Data; Databases; Development; Diet; Dietary Intervention; Dietary Practices; Disease; Evaluation; Experimental Genetics; Fostering; Foundations; Future; Genes; Genetic; Genetic Markers; Genetic Variation; Genome; Genomic Segment; Goals; Health; Human; Incidence; Individual; Japanese; Measurement; Mediation; Metabolic; Mission; Modeling; Molecular; Molecular Analysis; Mus; Nutritional Study; Outcome; Patients; Phenotype; Physiological; Play; Population; Precision Health; Public Health; Publishing; Recommendation; Research; Role; Sampling; Sensitivity and Specificity; Strategic Planning; System; Testing; Tissue Banks; United States National Institutes of Health; Vegan Diet; Work; base; cardiometabolism; cardiovascular health; clinical examination; clinical phenotype; data integration; data repository; data resource; dietary; dietary guidelines; epidemiologic data; feeding; genetic analysis; genetic architecture; human model; improved; innovation; ketogentic; molecular marker; molecular phenotype; mouse genetics; novel; nutrition; obesity prevention; precision nutrition; prevent; public database; repository; response; sex; tissue resource; trait; unpublished works; Address; American; Behavior; Behavior Therapy; Biological; Biological Markers; Cardiometabolic Disease; Characteristics; Communities; Data; Databases; Development; Diet; Dietary Intervention; Dietary Practices; Disease; Evaluation; Experimental Genetics; Fostering; Foundations; Future; Genes; Genetic; Genetic Markers; Genetic Variation; Genome; Genomic Segment; Goals; Health; Human; Incidence; Individual; Japanese; Measurement; Mediation; Metabolic; Mission; Modeling; Molecular; Molecular Analysis; Mus; Nutritional Study; Outcome; Patients; Phenotype; Physiological; Play; Population; Precision Health; Public Health; Publishing; Recommendation; Research; Role; Sampling; Sensitivity and Specificity; Strategic Planning; System; Testing; Tissue Banks; United States National Institutes of Health; Vegan Diet; Work; base; cardiometabolism; cardiovascular health; clinical examination; clinical phenotype; data integration; data repository; data resource; dietary; dietary guidelines; epidemiologic data; feeding; genetic analysis; genetic architecture; human model; improved; innovation; ketogentic; molecular marker; molecular phenotype; mouse genetics; novel; nutrition; obesity prevention; precision nutrition; prevent; public database; repository; response; sex; tissue resource; trait; unpublished works

PROJECT SUMMARY The incidence of cardiometabolic disease has soared during last half-century despite national efforts to improve health through universal dietary recommendations. A critical limitation of this approach is the lack of consideration given to dietary response differences based on an individual’s genetics, which is essential for the nascent field of precision nutrition. The long-term goal of this proposal is to develop the foundation and an experimental platform to support in-depth biological analyses of precision nutrition interventions. The objective of this proposal is to develop an experimental genetic reference platform that models human genetic diversity into a model for precision nutrition. Although largely relying on a discovery-driven approach, the central hypothesis is that a major failing of public health efforts has been generalization of dietary recommendations and that through matching dietary recommendations to an individual’s metabolic needs, cardiovascular health will be greatly improved at the individual and population level. This hypothesis is based on published and unpublished work. The rationale is that completion of these studies will identify genetic and metabolic factors and high-level mechanisms by which diet influences differential cardiometabolic health that can be used to develop new paradigms for precision nutrition. The proposed work will also provide a repository of data and samples from the Collaborative Cross, a publicly available mouse genetic reference population. The central hypothesis will be tested by pursuing three aims: 1) Identify cardiometabolic health traits that are influenced by gene-by-diet (GxD) interactions; 2) Determine the genetic architecture regulating diet-dependent effects on cardiometabolic health; and 3) Validate a precision nutrition paradigm to predict effects of diet on cardiometabolic disease. These aims will be pursued using an innovative combination of a novel, publicly available mouse genetic reference population and human relevant diets for which substantial epidemiological data exists on their cardiometabolic effects. The proposed research is significant because it will determine the health impact that individual genetic variation has on response to common diets and identify those characteristics that are influenced by GxD interactions. It is also significant because it will provide a public database of physiological responses and a sample repository of tissues for future molecular analyses, providing a critical foundation for the nascent field of precision nutrition. The expected outcome of this project is a comprehensive understanding of how diet influences cardiometabolic health in an experimental genetic reference population, an essential first step to support future projects in precision nutrition. The resulting data will have an important positive impact because it will provide a paradigm shift toward precision nutrition by: a) identifying cardiometabolic phenotypes influenced by GxD responses; b) elucidating the genetic architecture and high-level mechanisms of unique responses to diet; c) validating putative diet responses through confirmatory studies; and d) generating a rich database of GxD responses and a sample repository for use by the research community.

项目摘要 在最后半个世纪的全国努力中，心脏代谢疾病的事件飙升了 通过普遍的饮食建议健康。这种方法的关键限制是缺乏 考虑了基于个人遗传学的饮食反应差异的考虑，这对于 精确营养的新生场。该提议的长期目标是建立基础和 实验平台支持精确营养干预措施的深入生物学分析。目标 该建议的是开发一个实验性遗传参考平台，该平台模拟人类遗传多样性 成精确营养的模型。尽管很大程度上依赖于发现驱动的方法，但中心 假设是，公共卫生努力的主要失败是对饮食建议的普遍性和 通过将饮食建议符合个人的代谢需求，心血管健康将是 在个人和人口水平上大大提高。该假设基于已出版和未发表的 工作。理由是这些研究的完成将确定遗传和代谢因素以及高级 饮食影响差异心脏代谢健康的机制可用于开发新的 精确营养的范例。拟议的工作还将提供数据存储库和来自 协作十字架，公开可用的鼠标遗传参考人群。中心假设将是 通过追求三个目标测试：1）确定受基因by-diet影响（GXD）的心脏代谢健康特征（GXD） 互动； 2）确定调节饮食依赖性对心脏代谢健康的影响的遗传结构； 3）验证一种精确的营养范例，以预测饮食对心脏代谢疾病的影响。这些目标 将使用一种新颖的公开鼠标遗传参考人群的创新组合来追求 和人类相关饮食，其心脏代谢作用存在大量流行病学数据。 拟议的研究很重要，因为它将确定个人遗传变异的健康影响 关于对常见饮食的反应并确定受GXD相互作用影响的特征。也是 意义重大，因为它将提供一个物理响应的公共数据库和组织样本存储库 对于将来的分子分析，为精确营养的新生场提供了关键的基础。这 该项目的预期结果是对饮食如何影响心脏代谢的全面理解 在实验遗传参考人群中的健康，这是支持未来项目的重要第一步 精确营养。最终的数据将产生重要的积极影响，因为它将提供范式 通过：a）鉴定受GXD反应影响的心脏代谢表型； b） 阐明对饮食的独特反应的遗传结构和高级机制； c）验证推定 通过确认研究做出饮食反应； d）生成丰富的GXD响应数据库和样本 研究界使用的存储库。