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

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 终末期肾病 (ESKD) 是导致美国人口死亡的主要原因之一。近40% ESKD 是由糖尿病引起的，其自然病程包括三个过渡阶段： 1.) 发展 糖尿病； 2.) 糖尿病肾病（DKD）的发生； 3.) DKD 进展为终末期疾病。 尽管 ESKD 造成了公共卫生负担，但为保护 ESKD 患者的肾功能而采取的干预措施 糖尿病的影响有限。黑人和西班牙裔群体面临着更高的糖尿病负担，并且进展更快 ESKD 高于白人、非西班牙裔群体。健康的社会决定因素 (SDOH) 和其他环境因素 暴露（例如金属）是造成这些差异的重要因素。然而，连接机制 DKD 的环境暴露尚不清楚。将环境数据整合到多组学中的研究 需要一个框架，特别是在黑人和西班牙裔社区，他们遭受过度的 ESKD 和 终生承受不利环境暴露的负担。我们的目标是建立糖尿病和肾脏 疾病研究中心 (DSS) 由 300 名不同种族和族裔的成年人组成，其中 200 名患有 糖尿病（其中一半还患有肾脏疾病）和 100 名健康对照。我们的 DSS 将成为 旨在推进多组学技术在健康和疾病研究中的应用的合作倡议 祖先多样化的人群。我们将积极与该联盟合作开展可推广的研究 协议，范围从参与者招募到可以共享和的综合分析管道 部署在云端。为了成功招募 300 名研究参与者（目标 1），我们将利用我们现有的 招聘基础设施，利用创新的选择策略，丰富我们的样本 可能会跨 DKD 阶段过渡。 UIC肾脏精准中心将同时招募30例DKD病例 医学项目 (KPMP)，能够链接到丰富的 KPMP 肾组织病理学和多组学数据 DKD 病例的子样本。我们的样本将反映我们卫生系统的多样性，其中包括患者 人口主要是非白人（~80%）。我们将进一步利用我们广泛的临床研究 收集生物样本并获得有关环境暴露、结果、 以及其他协变量，持续三年每年一次（目标 2）。采集的血液样本将用于进行 所有研究参与者的基因组、表观基因组、转录组、蛋白质组和代谢组分析（目标 3）。利用与联盟合作开发的管道和综合分析协议，我们将 识别与环境暴露和肾脏组织病理学相关的分子谱并检查它们 与 DKD 课程每个阶段的关联（目标 4）。我们期望我们的 DSS 能够进行重要的研究 影响，为综合系统生物学的总体进步提供关键信息 研究方法并阐明 DKD 的新生物学机制和生物标志物。