Epidemiological links between chronic kidney disease (CKD), hypertension (HTN), and risk for cardiovascular disease (CVD) are established, specific mechanisms responsible for these amplified risks are not clear. A genetic basis for each of these maladies is apparent, but causative gene mechanisms have not been identified. Recent large genome-wide association/linkage (GWAS/GWLS) studies have identified multiple loci associated with risk for CKD, CVD or HTN. This Core will facilitate studies aimed at understanding the genetic mechanisms of CKD, CVD, and HTN individually, and/or exploring their shared pathways of genetic risk. Researchers are often unable to take advantage of these advances due to lack of access to required infrastructure and resources and also lack access to expertise in study design, genetic epidemiology and analytical approaches critical for successful discovery. The Renal Genomics Core (RGC) will capitalize on superb existing institutional resources at the Center for Human Genetics and the Center for Human Genome Variation, reducing barriers to critical core services for researcher who are interested in exploring the genetic basis of these problems.
We aim to: 1) Establish a pre-study consultation service as an entry point for investigators interested in carrying out cardio-renal genetic studies. Assistance in study design and coordination of study protocols with investigators, including power analyses, human subjects IRB preparation, programming and informatics will be provided. 2)Provide a standardized service for DNA isolation and storage, tissue banking and DNA allocation. 3)Provide assistance in carrying out molecular genetic studies. Access to technical capabilities and expertise for GWAS/GWLS and whole-genome/-exome sequencing. The RGC will carry out followup targeted Sanger sequencing for gene identification, raw results data management, quality control, statistical and bioinformatic analysis incorporating the latest advances in statistical and genomic methodology. RGC will provide users with comprehensive genomics services that can be effectively utilized regardless of level of experience. Access to powerful tools will promote advances in understanding the genetic architecture of the complex interactions of the kidney in CVD and HTN.
This application is highly relevant to public health as it addresses two major causes of morbidity and mortality in the US. Chronic kidney disease and coronary artery disease are serious public health concerns. CAD is the leading cause of the death in the US. CKD is a major risk factor for CAD and there is evidence of heritability for both maladies: Objectives of this O'Brien Center will be to facilitate research on the kidney in hypertension and the links between CKD and CV complications.
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