权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Integrative Omics, Chronic Kidney Disease, and Adverse Outcomes in Older Adults

综合组学、慢性肾病和老年人的不良后果

基本信息

批准号：
10163839
负责人：
JOSEF CORESH
金额：
$ 68.77万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-05-13 至 2022-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10163839
关键词：
Address Adult Adverse event Affect Age Albumins Albuminuria Ancillary Study Area Atherosclerosis Risk in Communities Benign Biological Biological Markers Blood Cardiac Cardiovascular Diseases Caring Case-Control Studies Cessation of life Chronic Kidney Failure Clinical Communities Complex CpG dinucleotide Creatinine DNA DNA Methylation Data Disease Disease Outcome Disease Progression Drug Targeting Echocardiography Elderly End stage renal failure Environmental Exposure Epigenetic Process Etiology Event Fibrosis Filtration Functional disorder Funding Funding Mechanisms Gene Expression Genes Genetic Genetic Variation Goals Grant Heart failure Heterogeneity Hospitalization Hour Individual Inflammation Intervention Kidney Letters Longterm Follow-up Measures Mendelian randomization Metabolic Methods Methylation Molecular Multiomic Data National Institute of Diabetes and Digestive and Kidney Diseases Network-based Outcome Participant Pathogenesis Pathway Analysis Pathway interactions Patients Persons Phenotype Physiology Population Prevention Production Prognosis Proteins Proteomics Renal function Research Priority Risk Risk Factors Series Signal Transduction Site Systems Biology Techniques Tissues Urine Variant Visit adjudicate adverse outcome age related aged atherosclerosis risk base clinical risk clinically relevant cohort disorder risk drug development epigenetic variation epigenome-wide association studies epigenomics experience genetic variant genome wide association study heart function high risk high throughput technology improved innovation insight interest metabolomics methylation pattern mortality novel prevent protein metabolite risk prediction therapeutic target therapy development

项目摘要

PROJECT SUMMARY Chronic kidney disease (CKD) affects 500 million people worldwide, with the greatest burden among older adults. People with CKD are at elevated risk for not only end-stage kidney disease, but also cardiovascular disease, heart failure, and death. Existing treatment for CKD is inadequate, and there is vast, poorly understood heterogeneity in disease progression. While genome-wide association studies have identified genetic variants that modulate CKD-associated risk, much of the hereditability of CKD, as well as the molecular basis for how identified variants regulate disease, remains unexplained. Our overarching hypothesis is that an integrated approach combining genetics, epigenetics, proteomics, and metabolomics can yield novel insights into the pathogenesis and prognosis of CKD. Variability in disease may be due in part to variability in DNA methylation, which changes with age and the metabolic milieu and can modify gene expression. Advances in high-throughput technology have revolutionized the breadth and precision of metabolomic and proteomic profiling, enabling unprecedented windows into trans-omic networks. The objective of this study is to use a systems biology approach to integrate genetic sequence variation with DNA methylation patterns, proteomics, and metabolomics in order to advance our understanding and treatment of CKD risk. The proposed grant will pursue biological pathways that affect CKD risk in the ongoing Atherosclerosis Risk Communities (ARIC) study, a contemporary, community-based cohort of white and black adults now aged 70 years and older, with plan for replication in two CKD cohorts and further extension to kidney tissue. The combination of rich phenotyping, comprehensive adjudicated outcomes, and genetic, epigenomic (funded by this grant), proteomic, and metabolomic data provides a unique opportunity to generate insights into the molecular basis of CKD, improve CKD risk prediction, and identify a series of candidate pathways and genes whose products may serve as targets for drug development. With the long-term goal of improving care in patients with CKD, we aim to discover associations between kidney function and metabolites, proteins, and related pathways (Aim 1), identifying specific pathways that provide insight into CKD-associated outcomes, including CKD progression, heart failure, cardiovascular disease, and mortality (Aim 2), and elucidate genetic and epigenetic variation underlying these candidate pathways (Aim 3). The study will use a combination of innovative methods and omics data to identify pathways and genetic variation that are clinical relevant and thus useful in informing the risk prediction and potentially treatment of patients with CKD.

项目总结