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Integrative genomic, epigenetic and functional studies in diabetic kidney disease

糖尿病肾病的综合基因组、表观遗传学和功能研究

基本信息

批准号：
9029513
负责人：
JOSE CARLOS FLOREZ
金额：
$ 84.58万
依托单位：
BROAD INSTITUTE, INC.
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-12-23 至 2019-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9029513
关键词：
Address Amputation Area Biological Biological Markers Biological Models Biological Process Biology Biopsy Blindness Blood Candidate Disease Gene Cell model Chronic Kidney Failure Code Collaborations Complement Complication Complications of Diabetes Mellitus DNA Methylation DNA Sequence Data Data Set Development Diabetes Mellitus Diabetic Nephropathy Disease End stage renal failure Epigenetic Process Frequencies Functional disorder Funding Funding Mechanisms Gene Expression Profiling Gene Targeting Genes Genetic Genetic study Genomics Guide prevention Health Care Costs Heart Diseases Heterogeneity Hyperglycemia Individual Inherited Institutes Insulin-Dependent Diabetes Mellitus Interdisciplinary Study International Investigation Ireland Kidney Kidney Diseases Kidney Failure Knowledge Letters Meta-Analysis Methods Methylation Microvascular Dysfunction Modeling Molecular Northern Ireland Organ Participant Pathogenesis Pathway interactions Patients Phenotype Play Positioning Attribute Prevention Prevention strategy Preventive measure Process Public Health Publishing Regulatory Element Renal function Research Resources Risk Risk Factors Role Sample Size Sampling Secondary to Severities Stroke Testing Translating Universities Untranslated RNA Validation Variant base diabetic exome exome sequencing follow-up genetic analysis genetic approach genetic association genetic risk factor genetic variant genome wide association study genomic data glycemic control human data improved insight macrovascular disease mortality multidisciplinary novel potential biomarker public health relevance rare variant trait

项目摘要

DESCRIPTION (provided by applicant): Diabetic kidney disease (DKD) is a leading cause of kidney failure and end stage renal disease, and brings a substantial burden of early mortality and accompanying health care costs. Genetic factors contribute to the risk of DKD. If we could identify these genetic factors, we could better understand the mechanisms by which DKD occurs, and thereby accelerate the development of better therapies. We established the GENIE consortium, a collaboration between Queen's University Belfast, University of Dublin, University of Helsinki, and the Broad Institute. Together, we completed the largest genetic study to date of DKD, and successfully identified the first two robust genetic risk factors for DKD. In a separately funded genetic study, we are collaborating with additional groups to extend our efforts and encompass larger samples. To better understand the underlying biology and pathophysiology of DKD, we propose to complement and build on our past and ongoing genetic studies in several critical ways. We will leverage a co-funding mechanism between Ireland, Northern Ireland and the US to carry out a multidisciplinary investigation of DKD. We will assemble and jointly analyze all available genetic data pertinent to DKD, to begin the process of discovering rarer variants with stronger effects on DKD. We will also generate DNA methylation data in kidney and blood, and in patients with and without DKD, and also expression data in samples relevant to DKD. We use a novel and powerful method to integrate the genetic, epigenetic and genomic data to generate hypotheses about the biological causes of DKD, and test these hypotheses with further genetic studies (sequencing in a large follow-up sample) and with functional studies in models of DKD. This international, multidisciplinary collaboration will build on genetic discoveries to help decipher the underlying biology and pathophysiology of DKD and thereby guide the prevention and treatment of this important disease.