Metabolomic predictors of stroke in REGARDS

REGARDS中中风的代谢组学预测因子

• 批准号: 10066373
• 负责人: William Taylor Kimberly
• 金额: $ 46.46万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-12-01 至 2022-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10066373
• 关键词: Accounting; Address; African American; Age; Amino Acids; Area; Arteries; Atrial Fibrillation; Attention; Biochemical; Biochemical Process; Bioinformatics; Biological; Biological Markers; Cerebrovascular Disorders; Clinical; Cohort Studies; Communities; Complex; Control Groups; Cross-Sectional Studies; Data; Disease; Epidemiology; Etiology; Folic Acid; Framingham Heart Study; Genetic; Genetic Risk; Genetic Variation; Genetic study; Geography; HDAC9 gene; Haplotypes; Heart; Heterogeneity; Homocysteine; Hypertension; Individual; Interdisciplinary Study; Ischemic Stroke; Jackson Heart Study; K-Series Research Career Programs; Knowledge; Laboratories; Link; Liquid Chromatography; Mass Spectrum Analysis; Mediation; Metabolic; Metabolic Pathway; Methods; Monitor; Observational Study; Pathway interactions; Phenotype; Population; Positioning Attribute; Prevention; Pseudouridine; Race; Randomized Controlled Trials; Reasons for Geographic And Racial Differences in Stroke; Research; Research Personnel; Resources; Risk; Risk Factors; Risk Marker; Role; Sampling; Southeastern United States; Stroke; Surveys; Techniques; Technology; Testing; Therapeutic; United States; Universities; Uridine; Validation; Variant; Work; acute stroke; base; burden of illness; case control; clinical risk; cohort; diet and exercise; ethnic difference; experience; folic acid supplementation; genetic variant; genome wide association study; genomic locus; health disparity; human disease; improved; innovation; insight; metabolomics; multi-ethnic; multi-racial; novel; population based; racial difference; racial disparity; sex; small molecule; stroke risk; tandem mass spectrometry; trait; translational research program

Abstract There is a disproportionate burden of stroke among African Americans (AA) and individuals in the Southeastern United States, although the environmental and/or genetic underpinnings remain incompletely defined. Because metabolites integrate both environmental and genetic factors, they serve as proximal markers of human disease. In prior work supported by a Career Development Award, we established a rapid, multifunctional metabolomics platform that can be applied to large epidemiological cohorts. We now seek to focus our study on the metabolite predictors of cerebrovascular disease, an area that has received relatively little attention. To address these gaps in knowledge, we propose conducting metabolomics in stroke in the multiethnic REasons for Geographic and Racial Differences in Stroke ( REGARDS) study, with further replication in the Jackson Heart Study (JHS) and Framingham Heart Study (FHS). We will test the overarching hypothesis that metabolomics in well-phenotyped populations will illuminate stroke-associated metabolite pathways, and unravel racial differences among them. In Aim 1, we will identify metabolite risk factors for incident stroke, stratified by subtype, in the case-control cohort of the REGARDS study. We will profile metabolites from the baseline examination in ~1200 incident stroke cases and ~1200 controls matched for age, sex and race. In Aim 2, we will identify novel metabolite markers of known clinical risk traits for stroke, including atrial fibrillation, hypertension, diet and exercise. In Aim 3, we will validate novel metabolite predictors of incident stroke and associated risk traits in the JHS and FHS cohorts. We will also test whether genetic variants that determine metabolite levels are in turn associated with clinical traits, through genetic risk score analysis. With extensive study data, the REGARDS study is uniquely positioned to catalyze the Aims of this proposal. Leveraging a novel small molecule profiling platform, our preliminary studies demonstrate the feasibility and significance of the Aims. Our multidisciplinary collaboration includes investigators at the MGH, UAB and University of Cincinnati, who bring collective expertise in metabolite profiling, biomarkers, genetic and population epidemiology, bioinformatics, metabolic traits, and health disparities. Finally, all data will be made publicly available, producing a unique scientific resource for the stroke research community.

抽象的 非裔美国人 (AA) 和美国人中的中风负担不成比例 美国东南部，尽管环境和/或遗传基础仍然不完全 定义的。由于代谢物整合了环境和遗传因素，因此它们充当近端因素 人类疾病的标志。在职业发展奖支持的先前工作中，我们建立了快速、 可应用于大型流行病学队列的多功能代谢组学平台。我们现在寻求 我们的研究重点是脑血管疾病的代谢物预测因子，这是一个相对较受关注的领域。 很少关注。为了解决这些知识差距，我们建议在中风中进行代谢组学 多民族的 中风的地理和种族差异的原因（ 问候）研究，进一步 杰克逊心脏研究 (JHS) 和弗雷明汉心脏研究 (FHS) 中的复制。我们将测试总体 假设表型良好的人群中的代谢组学将阐明中风相关代谢物 途径，并消除他们之间的种族差异。在目标 1 中，我们将确定代谢风险因素 REGARDS 研究的病例对照队列中，按亚型分层的中风事件。我们将简介 约 1200 例卒中病例和约 1200 例对照者的基线检查代谢物与年龄相匹配， 性别和种族。在目标 2 中，我们将鉴定已知中风临床风险特征的新代谢标志物， 包括心房颤动、高血压、饮食和运动。在目标 3 中，我们将验证新的代谢物 JHS 和 FHS 队列中卒中事件和相关风险特征的预测因素。我们还将测试是否 决定代谢水平的遗传变异反过来又通过遗传风险与临床特征相关 分数分析。凭借广泛的研究数据，REGARDS 研究具有独特的定位，可以促进以下目标的实现： 这个建议。利用新颖的小分子分析平台，我们的初步研究表明 目标的可行性和意义。我们的多学科合作包括 MGH 的研究人员、 UAB 和辛辛那提大学带来了代谢物分析、生物标志物、遗传和疾病方面的集体专业知识 人口流行病学、生物信息学、代谢特征和健康差异。最后将所有数据制作完成 公开可用，为中风研究界提供独特的科学资源。

项目成果

Intravenous Glibenclamide Reduces Lesional Water Uptake in Large Hemispheric Infarction.

静脉注射格列本脲可减少大面积半球梗塞的病变水摄取。

• DOI: 10.1161/strokeaha.119.026036
• 发表时间: 2019-09-20
• 期刊: Stroke
• 影响因子: 8.3
• 作者: P. Vorasayan;M. Bevers;L. Beslow;G. Sze;B. Molyneaux;H. Hinson;J. Simard;R. von Kummer;K. Sheth;W. Kimberly
• 通讯作者: W. Kimberly

Plasma Metabolites and Life's Simple 7 in REGARDS.

血浆代谢物和 Lifes Simple 7 的问候。

• 发表时间: 2024-05
• 影响因子: 8.3
• 作者: Kijpaisalratana, Naruchorn;Ament, Zsuzsanna;Patki, Amit;Bhave, Varun M;Jones, Alana C;Couch, Catharine A;Garcia Guarniz, Ana;Cushman, Mary;Long, D Leann;Judd, Suzanne E;Irvin, M Ryan;Kimberly, W Taylor
• 通讯作者: Kimberly, W Taylor

Expression of DEspR in acute intracerebral hemorrhage.

DEspR 在急性脑出血中的表达。

• DOI: 10.1016/j.jstrokecerebrovasdis.2022.106685
• 发表时间: 2022-08-22
• 期刊: Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association
• 作者: Riana L. Schleicher;Karen Li;R. Mylvaganam;M. Bevers;J. Goldstein;W. Kimberly
• 通讯作者: W. Kimberly

Critical Care Management of Acute Ischemic Stroke.

急性缺血性中风的重症监护管理。

• 发表时间: 2017-06
• 作者: Bevers, Matthew B;Kimberly, W Taylor
• 通讯作者: Kimberly, W Taylor

Comparative Analysis of Markers of Mass Effect after Ischemic Stroke.

缺血性中风后质量效应标志物的比较分析。

• 发表时间: 2018
• 作者: Ostwaldt, Ann;Battey, Thomas W K;Irvine, Hannah J;Campbell, Bruce C V;Davis, Stephen M;Donnan, Geoffrey A;Kimberly, W Taylor
• 通讯作者: Kimberly, W Taylor