Multi-Omics for Chronic Kidney Disease

慢性肾脏病的多组学

基本信息

批准号：
10744557
负责人：
KRZYSZTOF KIRYLUK
金额：
$ 83.67万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
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：
2023-09-12 至 2028-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10744557
关键词：
APOL1 gene Acceleration Address Affect African American African American population African ancestry Anemia Blood Bone Diseases Cardiovascular Diseases Caring Chronic Chronic Kidney Failure Classification Clinical Complex Data Diabetes Mellitus Diagnosis Disease Disparity Economic Factors Economics Education Electrolytes Ensure Environment Environmental Exposure Environmental Monitoring Epidemiology Epigenetic Process Equity Ethics Etiology Exclusion Exposure to Filtration Frequencies Genetic Genetic study Genomics Glomerular Filtration Rate Goals Health Heritability Hispanic Hispanic Populations Histologic Human Genetics Immune Immune System Diseases Individual Injury Injury to Kidney Intervention Studies Kidney Diseases Lead Leadership Life Lupus Malignant Neoplasms Metabolic dysfunction Metabolism Methods Minority Minority Groups Mission Molecular Molecular Disease Morbidity - disease rate Nephrology Outcome Participant Patients Pattern Phenotype Play Population Heterogeneity Positioning Attribute Prevalence Prospective Studies Prospective cohort Proteomics Protocols documentation Public Health Renal function Reproducibility of Results Research Research Design Risk Role Science Site Socioeconomic Factors Standardization Systemic disease Toxic Environmental Substances Toxicant exposure Underrepresented Minority Underrepresented Populations United States National Institutes of Health Urine Work burden of illness clinical care cohort comorbidity cost design disorder control disorder risk disorder subtype epidemiology study experience genetic predictors genetic risk factor genetic testing health equity promotion high risk high throughput technology hispanic community improved innovation kidney biopsy kidney dysfunction metabolomics molecular marker molecular subtypes mortality multidisciplinary multiple omics nephrotoxicity non-diabetic novel outreach pollutant precision medicine prospective recruit risk variant social social factors social health determinants statistics stressor support network transcriptomics

项目摘要

PROJECT SUMMARY Chronic kidney disease (CKD) is a common complex condition associated with high morbidity and mortality, with a prevalence estimated at 13% in the U.S. that continues to increase annually. The etiology of CKD is complex, with both genetic – including monogenetic and polygenic – and environmental contributions playing major roles. African American and Hispanic communities in the U.S. are disproportionally affected by CKD; environmental, socioeconomic, and inherited factors, such as APOL1 risk genotypes, are likely contributing to these disparities. Multi-omic approaches including genetics, epigenetics, transcriptomics, proteomics, and metabolomics are high- throughput technologies being leveraged for precision medicine that hold great potential to improve diagnosis and clinical care for complex diseases such as CKD. As part of the Multi-omics Health and Disease Consortium, this proposal will establish a Disease Study Site (DSS) focused on CKD. Our rationale for selecting CKD is three- fold: 1) CKD has high cost and public health impact in the U.S. and disproportionally affects minority populations underrepresented in genomic research; 2) CKD represents an important modifier of multi-omic profiles in other common conditions; and 3) there is an urgent, unmet need to provide molecular disease subclassification in CKD – and in particular non-diabetic CKD – as the current diagnosis relies solely on functional rather than molecular criteria. Our hypothesis is that longitudinal blood and urine multi-omics can provide non-invasive means to better subclassify non-diabetic CKD, and thus provide a new precision medicine-based approach for this condition. In alignment with the mission of the consortium, our DSS also aims to address current disparities in kidney disease and genomics, considering that individuals of non-European ancestry are overwhelming under-represented in human genetic and multi-omic studies of kidney disease. To this end, we propose a prospective study of 200 CKD patients and 100 non-CKD controls of diverse ancestral backgrounds, with at least 75% of participants from groups underrepresented in research. We will address the following questions: What are the molecular correlates of longitudinal decline in renal function in ancestrally diverse patients? Are there specific molecular subtypes of non-diabetic CKD identifiable by longitudinal multi-omics? What are the roles of environmental exposures, social and economic stressors, and genetics in determining molecular CKD subtypes? Our team involves national leaders in Precision Medicine and has a track record of successful execution of genetic, epidemiologic, and interventional studies involving diverse underrepresented populations. We will coordinate efficient local recruitment of our prospective cohort using innovative outreach methods that address barriers to recruiting under-represented groups. Our long-term goal is to promote health equity and challenge the existing clinical paradigms in CKD and multi-omics more broadly to advance precision medicine.

项目概要慢性肾脏病（CKD）是一种常见的复杂疾病，发病率和死亡率较高，在美国，CKD 的患病率估计为 13%，并且每年持续增加。 CKD 的病因很复杂，遗传（包括单基因和多基因）和环境贡献发挥着重要作用。美国的非裔美国人和西班牙裔社区受到 CKD 环境的影响尤为严重；失业和遗传因素（例如 APOL1 风险基因型）可能是造成这些差异的原因。包括遗传学、表观遗传学、转录组学、蛋白质组学和代谢组学在内的多组学方法具有很高的应用前景。通量技术被用于精准医学，在改善诊断方面具有巨大潜力作为多组学健康与疾病联盟的一部分，该提案将建立一个专注于 CKD 的疾病研究中心 (DSS) 我们选择 CKD 的理由是三个：折叠：1) CKD 在美国具有很高的成本和公共健康影响，并且对少数族裔人口产生不成比例的影响 2) CKD 代表了其他领域多组学概况的重要修饰剂常见病症；3) 提供 CKD 分子疾病亚分类的迫切需求尚未得到满足 – 特别是非糖尿病 CKD – 因为目前的诊断仅依赖于功能而非分子我们的假设是，纵向血液和尿液多组学可以提供非侵入性手段来更好地进行研究。对非糖尿病 CKD 进行细分，从而为这种疾病提供一种新的基于精准医学的方法。与联盟的使命保持一致，我们的 DSS 还旨在解决当前肾脏疾病方面的差异和基因组学，考虑到非欧洲血统的个体在为此，我们提出了一项针对 200 项肾脏疾病的前瞻性研究。 CKD 患者和 100 名不同祖先背景的非 CKD 对照，其中至少 75% 的参与者来自我们将解决以下问题：分子相关性是什么？祖先不同的患者肾功能纵向下降是否存在特定的分子亚型？通过纵向多组学可识别非糖尿病 CKD 环境暴露、社会因素有何作用？和经济压力以及遗传学来确定分子 CKD 亚型？精准医学领域的领导者，并拥有成功执行遗传、流行病学和我们将协调有效的当地群体的干预研究。使用创新的外展方法来招募我们的潜在队列，以解决招募障碍我们的长期目标是促进健康公平并挑战现有的临床。 CKD 和多组学领域更广泛的范例，以推进精准医学。