End Stage Renal Disease (ESRD)NCT00559767
Mapping of End Stage Renal Disease Genetic Susceptibility in African Americans by Admixture Linkage Disequilibrium
An observational study of End Stage Renal Disease (ESRD), run by National Cancer Institute (NCI) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 years and older
- Conditions the study is for
- End Stage Renal Disease (ESRD)
- How many people
- 2,860 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Jun 2006to 10 Apr 2012
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- Children and all ethnicities other than African - American, African, and European will be excluded from this study.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Cancer Institute (NCI), 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
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.
Read the detailed description
Background:
- 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.
Objectives:
- 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.
Eligibility:
- 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.
Design:
- 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.
- Conditions
- End Stage Renal Disease (ESRD)
- Keywords
- Kidney Function, Genes, Association Analysis, Polymorphisms, Diabetes
- Medical subject headings
- Kidney Failure, Chronic, Diabetes Mellitus
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Nov 2007 (estimated)
- Study start30 Jun 2006
- Study completion10 Apr 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for End Stage Renal Disease (ESRD)Studies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Enrolment
- 2,860 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Investigators
- Martha Linet, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00559767
- Sponsor's protocol ID
- 999906210
- Other IDs
- 06-C-N210
- Status last verified
- 10 Apr 2012
- First submitted
- 15 Nov 2007
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
Patterson N, Hattangadi N, Lane B, Lohmueller KE, Hafler DA, Oksenberg JR, Hauser SL, Smith MW, O'Brien SJ, Altshuler D, Daly MJ, Reich D. Methods for high-density admixture mapping of disease genes. Am J Hum Genet. 2004 May;74(5):979-1000. doi: 10.1086/420871. Epub 2004 Apr 14.
PubMed 15088269Smith MW, Patterson N, Lautenberger JA, Truelove AL, McDonald GJ, Waliszewska A, Kessing BD, Malasky MJ, Scafe C, Le E, De Jager PL, Mignault AA, Yi Z, De The G, Essex M, Sankale JL, Moore JH, Poku K, Phair JP, Goedert JJ, Vlahov D, Williams SM, Tishkoff SA, Winkler CA, De La Vega FM, Woodage T, Sninsky JJ, Hafler DA, Altshuler D, Gilbert DA, O'Brien SJ, Reich D. A high-density admixture map for disease gene discovery in african americans. Am J Hum Genet. 2004 May;74(5):1001-13. doi: 10.1086/420856. Epub 2004 Apr 14.
PubMed 15088270Smith MW, Lautenberger JA, Shin HD, Chretien JP, Shrestha S, Gilbert DA, O'Brien SJ. Markers for mapping by admixture linkage disequilibrium in African American and Hispanic populations. Am J Hum Genet. 2001 Nov;69(5):1080-94. doi: 10.1086/323922.
PubMed 11590548
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mapping of End Stage Renal Disease Genetic Susceptibility in African Americans by Admixture Linkage Disequilibrium
- ClinicalTrials.gov ID
- NCT00559767
- Acronym / sponsor ID
- 999906210
- Conditions
- End Stage Renal Disease (ESRD)
- Keywords
- Kidney Function, Genes, Association Analysis, Polymorphisms, Diabetes
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 2,860 participants (estimated)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 30 Jun 2006
- Study completion
- 10 Apr 2012
- First posted
- 16 Nov 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Background:
- 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.
Objectives:
- 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.
Eligibility:
- 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.
Design:
- 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
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (1 listed)
- Children and all ethnicities other than African - American, African, and European will be excluded from this study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2017.
- Background: PubMed 15088269Patterson N, Hattangadi N, Lane B, Lohmueller KE, Hafler DA, Oksenberg JR, Hauser SL, Smith MW, O'Brien SJ, Altshuler D, Daly MJ, Reich D. Methods for high-density admixture mapping of disease genes. Am J Hum Genet. 2004 May;74(5):979-1000. doi: 10.1086/420871. Epub 2004 Apr 14.
- Background: PubMed 15088270Smith MW, Patterson N, Lautenberger JA, Truelove AL, McDonald GJ, Waliszewska A, Kessing BD, Malasky MJ, Scafe C, Le E, De Jager PL, Mignault AA, Yi Z, De The G, Essex M, Sankale JL, Moore JH, Poku K, Phair JP, Goedert JJ, Vlahov D, Williams SM, Tishkoff SA, Winkler CA, De La Vega FM, Woodage T, Sninsky JJ, Hafler DA, Altshuler D, Gilbert DA, O'Brien SJ, Reich D. A high-density admixture map for disease gene discovery in african americans. Am J Hum Genet. 2004 May;74(5):1001-13. doi: 10.1086/420856. Epub 2004 Apr 14.
- Background: PubMed 11590548Smith MW, Lautenberger JA, Shin HD, Chretien JP, Shrestha S, Gilbert DA, O'Brien SJ. Markers for mapping by admixture linkage disequilibrium in African American and Hispanic populations. Am J Hum Genet. 2001 Nov;69(5):1080-94. doi: 10.1086/323922.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Martha Linet, M.D. principal investigator
National Cancer Institute (NCI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of End Stage Renal Disease (ESRD), run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00559767, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2017; AzTrials last refreshed its copy on 8 Nov 2026.