Multi-Omics at the Intersections of Environment, Diabetes, and Kidney Disease: A Multi-Omics for Health and Disease Study Site

环境、糖尿病和肾脏疾病交叉点的多组学：健康和疾病研究网站的多组学

• 批准号: 10744464
• 负责人: Maria Argos
• 金额: $ 81.15万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-12 至 2028-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10744464
• 关键词: Adult; Affect; Biological; Biological Markers; Black Populations; Black race; Blood; Blood specimen; Chicago; Chronic Kidney Failure; Clinical Research; Collaborations; Collection; Data; Data Collection; Data Linkages; Development; Diabetes Mellitus; Diabetic Nephropathy; Disease; Disease Progression; Disparity; Ecosystem; Electronic Health Record; End stage renal failure; Environment; Environmental Exposure; Exposure to; Face; Generations; Genomics; Goals; Health; Health Sciences; Health system; Hispanic; Hispanic Populations; Histopathology; Hospitals; Illinois; Informatics; Infrastructure; Intervention; Kidney; Kidney Diseases; Link; Measures; Metals; Methods; Mission; Molecular; Molecular Profiling; Multiomic Data; National Human Genome Research Institute; Natural History; Not Hispanic or Latino; Outcome; Participant; Patient Recruitments; Patients; Pharmaceutical Preparations; Phenotype; Population; Population Heterogeneity; Precision Health; Process; Proteomics; Protocols documentation; Public Health; Renal function; Renin-Angiotensin-Aldosterone System; Research; Research Methodology; Residual state; Risk; Role; Sampling; Site; System; Systems Biology; Technology; Testing; Time; Tissues; Universities; Variant; Visualization; Work; analytical method; blood glucose regulation; blood pressure control; cloud based; cohort; data analysis pipeline; disorder prevention; effective intervention; eligible participant; end stage disease; epigenomics; ethnic diversity; experience; hispanic community; innovation; kidney preservation; metabolomics; mortality; multidisciplinary; multiple omics; novel; novel strategies; patient population; peripheral blood; precision medicine; protocol development; racial diversity; recruit; social health determinants; transcriptomics; Adult; Affect; Biological; Biological Markers; Black Populations; Black race; Blood; Blood specimen; Chicago; Chronic Kidney Failure; Clinical Research; Collaborations; Collection; Data; Data Collection; Data Linkages; Development; Diabetes Mellitus; Diabetic Nephropathy; Disease; Disease Progression; Disparity; Ecosystem; Electronic Health Record; End stage renal failure; Environment; Environmental Exposure; Exposure to; Face; Generations; Genomics; Goals; Health; Health Sciences; Health system; Hispanic; Hispanic Populations; Histopathology; Hospitals; Illinois; Informatics; Infrastructure; Intervention; Kidney; Kidney Diseases; Link; Measures; Metals; Methods; Mission; Molecular; Molecular Profiling; Multiomic Data; National Human Genome Research Institute; Natural History; Not Hispanic or Latino; Outcome; Participant; Patient Recruitments; Patients; Pharmaceutical Preparations; Phenotype; Population; Population Heterogeneity; Precision Health; Process; Proteomics; Protocols documentation; Public Health; Renal function; Renin-Angiotensin-Aldosterone System; Research; Research Methodology; Residual state; Risk; Role; Sampling; Site; System; Systems Biology; Technology; Testing; Time; Tissues; Universities; Variant; Visualization; Work; analytical method; blood glucose regulation; blood pressure control; cloud based; cohort; data analysis pipeline; disorder prevention; effective intervention; eligible participant; end stage disease; epigenomics; ethnic diversity; experience; hispanic community; innovation; kidney preservation; metabolomics; mortality; multidisciplinary; multiple omics; novel; novel strategies; patient population; peripheral blood; precision medicine; protocol development; racial diversity; recruit; social health determinants; transcriptomics

ABSTRACT End stage kidney disease (ESKD) is among the top contributors to mortality in the US population. Nearly 40% of ESKD is caused by diabetes, with a natural history that includes three transitional stages: 1.) Development of diabetes; 2.) Initiation of diabetic kidney disease (DKD); and 3.) Progression of DKD to end-stage disease. Despite the public health burden posed by ESKD, interventions to preserve kidney function in patients with diabetes are limited. Black and Hispanic groups face higher burdens of diabetes and more rapid progression to ESKD than White, non-Hispanic groups. Social determinants of health (SDOH) and other environmental exposures (e.g., metals) are important contributors to these disparities. However, the mechanisms linking environmental exposures to DKD are unclear. Research to integrate environmental data into the multi-omics framework is needed, particularly in Black and Hispanic communities, who suffer from excessive ESKD and are burdened by life-long, adverse environmental exposures. Our goal is to establish a diabetes and kidney disease study site (DSS) comprised of 300 racially and ethnically diverse adults, including 200 with diabetes (half of whom also have kidney disease) and 100 healthy controls. Our DSS will be part of a collaborative initiative to advance the application of multi-omics technologies to study health and disease in ancestrally diverse populations. We will actively engage with this consortium to develop generalizable study protocols, ranging from participant recruitment to integrative analytic pipelines that can be shared and deployed in the cloud. To successfully recruit 300 study participants (Aim 1), we will leverage our established recruitment infrastructure, utilizing an innovative selection strategy that will enrich our sample for those most likely to transition across DKD stages. Thirty DKD cases will be dually recruited with the UIC Kidney Precision Medicine Project (KPMP), enabling linkage to rich KPMP kidney tissue histopathology and multi-omics data in a subsample of DKD cases. Our sample will reflect the diversity of our health system, which includes a patient population that is predominantly non-White (~80%). We will further leverage our extensive clinical research experience to collect biospecimens and obtain detailed information on environmental exposures, outcomes, and other covariables annually for three years (Aim 2). Collected blood specimens will be used to carry-out genomic, epigenomic, transcriptomic, proteomic, and metabolomic profiling among all study participants (Aim 3). Utilizing pipelines and integrative analytic protocols developed in collaboration with the consortium, we will identify molecular profiles linked to environmental exposures and kidney histopathology and examine their associations with each stage of the DKD course (Aim 4). We expect our DSS to have important research impacts, contributing critical information towards the general advancement of integrative systems biology research methods and elucidating novel biological mechanisms and biomarkers for DKD.

抽象的 末期肾脏疾病（ESKD）是美国人口死亡率的主要贡献者之一。近40％ ESKD是由糖尿病引起的，其自然历史包括三个过渡阶段：1。）发展 糖尿病； 2.）糖尿病肾脏疾病（DKD）的启动； 3.）DKD向末期疾病的进展。 尽管ESKD造成了公共卫生负担，但仍在 糖尿病有限。黑人和西班牙裔群体面临着较高的糖尿病负担，进展更快 ESKD多于白人，非西班牙裔群体。健康的社会决定因素（SDOH）和其他环境 暴露（例如金属）是这些差异的重要贡献者。但是，链接的机制 对DKD的环境暴露尚不清楚。研究将环境数据整合到多媒体中 需要框架，尤其是在黑人和西班牙裔社区中，他们的ESKD和 受到终身不利的环境暴露的负担。我们的目标是建立糖尿病和肾脏 疾病研究地点（DSS）由300种种族和种族多样化的成年人组成，其中包括200个 糖尿病（一半也患有肾脏疾病）和100个健康对照。我们的DSS将成为 协作倡议促进多态技术在研究健康和疾病中的应用 祖先多样化的人群。我们将积极与该财团合作以开发可概括的研究 协议，从参与者招聘到可以共享的综合分析管道， 部署在云中。为了成功招募300名研究参与者（AIM 1），我们将利用我们的已建立 招聘基础设施，利用一种创新的选择策略，可以丰富我们最喜欢的人的样本 可能在DKD阶段过渡。三十dkd案件将以UIC肾脏精度进行双重招募 医学项目（KPMP），使毕马威（KPMP DKD案例的子样本。我们的样本将反映我们的卫生系统的多样性，其中包括患者 主要是非白人的人口（约80％）。我们将进一步利用我们广泛的临床研究 经验收集生物测量并获取有关环境暴露，结果的详细信息 以及其他每年三年的协变量（AIM 2）。收集的血标本将用于携带 所有研究参与者之间的基因组，表观基因组，转录组，蛋白质组学和代谢组分析（AIM 3）。利用与财团合作制定的管道和综合分析协议，我们将 确定与环境暴露和肾脏组织病理学相关的分子特征并检查其 与DKD课程的每个阶段的关联（AIM 4）。我们希望我们的DSS有重要的研究 影响，为综合系统生物学的总体发展提供关键信息 研究方法和DKD的新型生物学机制和生物标志物。