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Mapping of End Stage Renal Disease Genetic Susceptibility in African Americans by Admixture Linkage Disequilibrium

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ClinicalTrials.gov Identifier: NCT00559767
Recruitment Status : Completed
First Posted : November 16, 2007
Last Update Posted : July 2, 2017
Information provided by:

Study Description
Brief Summary:

This study will identify which regions on the genes, and genes themselves, may account for an increased risk of end stage renal disease (ESRD), that is, near-total loss of kidney function, for people of African American descent. Researchers will use a technique called admixture linkage disequilibrium (MALD) to study genomes, genetic material, in about 2,500 participants from two existing studies and participants who will serve as controls. ESRD disproportionately affects African Americans, who constitute 29% of all ESRD patients in the Medicare ESRD program. The disease can result from a variety of diseases, with diabetes as the leading underlying cause (44% of cases) and hypertension as the second leading cause (26%). The proportion of ESRD cases caused by diabetes has increased dramatically.

Patients age 18 and older who are African American, who have ESRD, and who are participants of the FIND and CHOICE studies may be eligible for this study. FIND, or Family Investigation of Diabetes and Nephropathy, involves a multicenter study to identify susceptibility genes, that is, those with a risk, for diabetic and other forms of kidney disease. CHOICE, or Choices for Healthy Outcomes in Caring for ESRD patients is an ongoing study that identifies risk factors for cardiovascular outcomes in ESRD patients. The principle of mapping by MALD involves genetic variations that exist across populations. When mixing occurs between populations having different (heterogeneous) genes, the admixed offspring inherits chromosomes of distinct ancestry. However, over generations of mating, and recombination over several generations, originally large blocks of DNA from African ancestry have become part of smaller segments throughout the chromosome. The study will focus on risk alleles, that is, alternative forms of genes that carry a disease risk. Risk alleles are closely related to nearby ancestral gene markers found in a person.

Patients will undergo a collection of blood and urine for genetic testing. Researchers are conducting separate analyses in this study. Case-control analysis of ESRD will consist of 1,150 participants from FIND and 250 from CHOICE. There will also be 750 control participants from FIND. For the case-control analysis of diabetic ESRD, there will be about 750 participants from FIND, 125 from CHOICE, and 750 controls from FIND. Finally, there is the quantitative trait analysis, which looks at the phenotype-meaning visible characteristics produced by the interaction of a person's genetic makeup with the environment. That analysis will involve 350 patients with diabetic nephropathy but not ESRD and 750 controls from FIND.

Condition or disease
End Stage Renal Disease (ESRD)

Detailed Description:


  • End stage renal disease (ESRD) is the near-total loss of kidney function which can result from a variety of diseases. ESRD disproportionately affects African Americans; this group comprises 29% of all ESRD patients treated in the Medicare ESRD program, a proportion that markedly exceeds their representation in the general population.
  • The Family Investigation of Diabetes and Nephropathy (FIND) study is an ongoing study to identify susceptibility genes for diabetic and other forms of nephropathy, and the Choices for Healthy Outcomes in Caring for ESRD patients (CHOICE) study is an ongoing prospective study to identify risk factors for cardiovascular outcomes in ESRD patients. Participants of these studies have already been recruited and characterized with respect to renal phenotypes; furthermore, DNAs from these individuals have already been collected and isolated. In this study, we intend to genotype markers suitable for MALD analysis in African Americans. The central hypothesis of the present study is that some renal disease susceptibility alleles are present at higher frequency in African Americans than in whites and that specific regions of the genome in African Americans contain marker alleles that are in admixture linkage disequilibrium with ESRD susceptibility alleles.


  • The overall objective of this study is to identify novel loci, genes, and gene products, that may partially account for excess risk of end stage renal disease (ESRD) in African Americans compared to whites.
  • To achieve this goal, we will employ Mapping by Admixture Linkage Disequilibrium (MALD) analysis, a specialized form of linkage disequilibrium mapping, to perform a genome-wide association study in approximately 2,500 African-American participants from the FIND and CHOICE studies.


  • Specific Inclusion/Exclusion criteria: African American
  • Gender and minority inclusion. The FIND and CHOICE studies are open to both men and women of any ethnicity; however, due to the underlying principle of MALD analysis, this study will only include African-American participants of these cohorts.


  • Genotype 1536 African-American MALD markers (2 cM average spacing) utilizing DNA from approximately 2,500 African-American participants in FIND and CHOICE.
  • Perform a genome-wide association analysis utilizing a 2 cM dense genetic map and identify chromosomal loci that are in admixture linkage disequilibrium with:

    • ESRD in a case-control design
    • ESRD attributable to diabetes in a case-control design
    • Quantitative renal phenotypes
  • Fine map putative chromosomal region in admixture linkage disequilibrium with ESRD with densely-spaced single nucleotide polymorphisms.
  • A characterization of the MYH9 gene, its mRNA and the proteins encoded is planned for cases and controls. Gene sequencing of the region implicated will be undertaken. Characterization of mRNA products for quantities and alternative splicing will be evaluated. Experimental characterization of the MYH9 proteins for isoforms, post-translational modifications, interactions, and immunohistochemical staining will be performed.

Study Design

Study Type : Observational
Estimated Enrollment : 2860 participants
Official Title: Mapping of End Stage Renal Disease Genetic Susceptibility in African Americans by Admixture Linkage Disequilibrium
Study Start Date : June 30, 2006
Estimated Study Completion Date : April 10, 2012

Groups and Cohorts

Outcome Measures

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

The cohorts utilized in this study, FIND and CHOICE, are open to adults of both genders and any ethnicity. However, we will select and utilize only those samples from African - American participants. We will also utilize African (Yorban) and European controls for genotyping from the NIGMS HGCR.


Children and all ethnicities other than African - American, African, and European will be excluded from this study.

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00559767

United States, Maryland
National Cancer Institute (NCI), 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Cancer Institute (NCI)
Principal Investigator: Martha Linet, M.D. National Cancer Institute (NCI)
More Information

ClinicalTrials.gov Identifier: NCT00559767     History of Changes
Other Study ID Numbers: 999906210
First Posted: November 16, 2007    Key Record Dates
Last Update Posted: July 2, 2017
Last Verified: April 10, 2012

Keywords provided by National Institutes of Health Clinical Center (CC):
Kidney Function
Association Analysis

Additional relevant MeSH terms:
Kidney Diseases
Kidney Failure, Chronic
Disease Susceptibility
Genetic Predisposition to Disease
Urologic Diseases
Renal Insufficiency, Chronic
Renal Insufficiency
Disease Attributes
Pathologic Processes