Statistical methods for analysis of high-dimensional mediation pathways
高维中介路径分析的统计方法
基本信息
- 批准号:10582932
- 负责人:
- 金额:$ 34.47万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-04-19 至 2027-01-31
- 项目状态:未结题
- 来源:
- 关键词:AddressAdolescenceAdolescent obesityAffectAgeAlgorithmsAreaBehaviorBiological MarkersBiological ProcessBloodBody CompositionCenters for Disease Control and Prevention (U.S.)ChildChild HealthChronicChronic DiseaseClinical PathwaysClinical ResearchComplexComputer softwareDNA MethylationDataData AnalysesDevelopmentDietDimensionsDiseaseDisease PathwayDisease modelEconomicsEnvironmental ExposureEpigenetic ProcessEquationExposure toFoundationsFundingGoalsGraphGrowth and Development functionHandHealthHumanInterventionLifeLife StyleLiteratureLongevityMeasurementMediationMediatorMethodological StudiesMethodologyMethodsModelingMolecularNutritionalObesityOutcomeParameter EstimationPathway interactionsPhenotypePoliciesPregnancyPreventionProcessResearchResearch MethodologyRisk FactorsSample SizeScienceScientistSexual MaturationSiteSocioeconomic StatusStatistical MethodsStatistical ModelsStatistical StudyTechnologyTestingTranslational ResearchUnited States National Institutes of HealthUpdateadolescent health outcomesclinical translationcognitive functiondisorder preventioneconomic determinantexperimental studyhealth disparityhealth equalityhealth inequalitieshealth practicehigh dimensionalityhigh throughput technologyhuman diseaseimprovedinnovationinterestlipid biosynthesislipid metabolismlipidomemetabolomicsmethylation biomarkermolecular markermultidimensional datanovelobesity developmentonline tutorialoperationoutcome disparitiessimulationsocialsocioeconomicsstressortargeted biomarkertheoriesuser friendly software
项目摘要
Abstract
This proposal harnesses statistical theory and applications underlying mechanistic models to
study mediation pathways involving high-dimensional omics markers on the children growth and
development. This proposal aims to advance novel methodology, algorithms, and software to
improve the understanding of mechanistic effects of environmental perturbations and
socioeconomic stressors on biological processes related to children’s health outcomes such as
adolescent obesity, cognitive function, and sexual maturation. This project is the first to
systematically study the foundation of an emerging best-subset statistical estimation and
inference in high-dimensional structural equation models (SEMs), and the resulting analytic
toolboxes allow practitioners to simultaneously cluster, estimate, and validate key mediation
pathways of clinical importance. (i) We develop a new analytic paradigm that can jointly
process a large number of mediators (e.g. metabolites or DNA methylation CpG sites) to unveil
mechanistic mediation pathways with well-controlled false discovery rate. The methodology
innovation lies in a simultaneous operation of high-dimensional pathway clustering, parameter
estimation and inference in the high-dimensional SEMs with little estimation bias and no
compromise on false discovery. (ii) We develop an adaptive hypothesis testing methodology in
high-dimensional SEMs to perform statistical inference for mediation pathways with a proper
type I error control. This new method is deemed for significant power improvement over existing
methods. (iii) We investigate mediation effects of the maternal blood lipidome and DNA
methylation markers for the relationship of gestational environmental and socioeconomic
exposures on children’s health outcomes. Moreover, discovered mechanistic mediation
pathways will help develop potential interventions for better children’s health. (iv) We develop,
test, distribute, and support freely available implementations of the proposed methods in this
proposal. The developed statistical toolboxes can facilitate the translational clinical studies.
摘要
这一建议利用统计理论和应用程序的基础机制模型,
研究调解途径,涉及高维组学标记对儿童的生长和
发展该提案旨在推进新的方法、算法和软件,
提高对环境扰动的机械效应的认识,
与儿童健康结果有关的生物过程的社会经济压力因素,
青少年肥胖、认知功能和性成熟。该项目是第一个
系统地研究新兴的最佳子集统计估计的基础,
高维结构方程模型(SEM)中的推理,以及由此产生的分析
工具箱允许从业者同时对关键中介进行聚类、评估和验证
临床重要性的途径。(i)我们开发了一种新的分析范式,
处理大量介质(例如代谢物或DNA甲基化CpG位点),以揭示
具有良好控制的错误发现率的机械调解途径。的方法
创新在于同时操作高维路径聚类、参数
估计和推理的高维SEM几乎没有估计偏差和没有
对虚假发现的妥协(ii)我们开发了一种自适应假设检验方法,
高维SEM进行统计推断调解途径与适当的
第一类错误控制这种新的方法被认为是显着的功率改善,比现有的
方法. (iii)我们研究了母体血脂和DNA的介导作用
妊娠环境与社会经济关系的甲基化标记物
暴露对儿童健康的影响。此外,发现了机械调解
路径将有助于制定潜在的干预措施,以改善儿童健康。(iv)我们发展,
测试,分发和支持免费提供的方法的实现,
提议开发的统计工具箱可以促进转化临床研究。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Karen Eileen Peterson其他文献
Karen Eileen Peterson的其他文献
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{{ truncateString('Karen Eileen Peterson', 18)}}的其他基金
Metabolic Health Risk Among Mid-Life Women: The Roles of Toxicants, Inflammation, and Epigenetics
中年女性的代谢健康风险:毒物、炎症和表观遗传学的作用
- 批准号:
10659071 - 财政年份:2020
- 资助金额:
$ 34.47万 - 项目类别:
Metabolic Health Risk Among Mid-Life Women: The Roles of Toxicants, Inflammation, and Epigenetics
中年女性的代谢健康风险:毒物、炎症和表观遗传学的作用
- 批准号:
10430262 - 财政年份:2020
- 资助金额:
$ 34.47万 - 项目类别:
Metabolic Health Risk Among Mid-Life Women: The Roles of Toxicants, Inflammation, and Epigenetics
中年女性的代谢健康风险:毒物、炎症和表观遗传学的作用
- 批准号:
10269915 - 财政年份:2020
- 资助金额:
$ 34.47万 - 项目类别:
E3Gen: Multigenerational Effects of Toxicant Exposures on Life Course Health and Neurocognitive Outcomes in the ELEMENT Birth Cohorts
E3Gen:有毒物质暴露对 ELEMENT 出生队列生命周期健康和神经认知结果的多代影响
- 批准号:
10432260 - 财政年份:2017
- 资助金额:
$ 34.47万 - 项目类别:
E3Gen: Multigenerational Influences of Social Structure on Toxicant Exposures and Life Course Health in the ELEMENT Cohort
E3Gen:社会结构对 Element 队列中有毒物质暴露和生命过程健康的多代影响
- 批准号:
10584016 - 财政年份:2017
- 资助金额:
$ 34.47万 - 项目类别:
E3Gen: Multigenerational Effects of Toxicant Exposures on Life Course Health and Neurocognitive Outcomes in the ELEMENT Birth Cohorts
E3Gen:有毒物质暴露对 ELEMENT 出生队列生命周期健康和神经认知结果的多代影响
- 批准号:
10207628 - 财政年份:2017
- 资助金额:
$ 34.47万 - 项目类别:
E3Gen: Multigenerational Effects of Toxicant Exposures on Life Course Health and Neurocognitive Outcomes in the ELEMENT Birth Cohorts
E3Gen:有毒物质暴露对 ELEMENT 出生队列生命周期健康和神经认知结果的多代影响
- 批准号:
10201826 - 财政年份:2017
- 资助金额:
$ 34.47万 - 项目类别:
Prenatal and Childhood Exposure to Fluoride and Neurodevelopment
产前和儿童期接触氟化物与神经发育
- 批准号:
8271682 - 财政年份:2012
- 资助金额:
$ 34.47万 - 项目类别:
Project 1: Prenatal Lead Exposure, Early Childhood Growth, and Sexual Maturation
项目 1:产前铅暴露、儿童早期生长和性成熟
- 批准号:
8376827 - 财政年份:2012
- 资助金额:
$ 34.47万 - 项目类别:
Project 1: Prenatal Lead Exposure, Early Childhood Growth, and Sexual Maturation
项目 1:产前铅暴露、儿童早期生长和性成熟
- 批准号:
8250363 - 财政年份:2011
- 资助金额:
$ 34.47万 - 项目类别:
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