Genetic Modifiers of Cystic Fibrosis: Sibling Study

NCT ID: NCT00037778

Last Updated: 2016-08-31

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

3459 participants

Study Classification

OBSERVATIONAL

Study Start Date

2001-09-30

Study Completion Date

2013-02-28

Brief Summary

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The purpose of this study is to identify modifier genes in cystic fibrosis (CF).

Detailed Description

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BACKGROUND:

CF is a highly variable but inevitably fatal single gene disorder. Several lines of evidence suggest that genetic background contributes to the variability of cystic fibrosis phenotypes. The study will develop CF as a model for the identification of modifier genes by capitalizing on the availability of a large motivated population of affected twins and siblings.

The study is in response to a Request for Applications titled "Genetic Modifiers of Single Gene Defect Diseases" released in August 2000 and co-sponsored by the National Institute of Diabetes, Digestive, and Kidney Diseases.

DESIGN NARRATIVE:

The study has four aims: 1. To identify heritable CF phenotypes by twin study. Intrapair and interpair variance will be determined for selected CF phenotypes, and interclass correlations (monozygotic versus dizygotic) will be performed to identify CF phenotypes with a substantial heritable component. 2. To determine the contribution of genetic and other factors to the variability of CF phenotypes by analysis of affected sibs. Variance component methods will be used to evaluate the CF phenotypes that appear to be heritable based upon other studies or the results of aim 1. 3. To identify biologic phenotypes that correlate with heritable CF phenotypes by clinical study of twins and sibs. Multivariate analysis will be used to find biologic phenotypes associated with CF phenotypes. 4. To identify modifier genes and loci responsible for heritable CF phenotypes by linkage approaches. Identity by descent and transmission disequilibrium methods will be used to test linkage between candidate genes/loci and heritable CF phenotypes. To identify novel loci, genome-wide scans will be performed upon sib pairs selected for extreme concordance or discordance for heritable traits.

Conditions

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Lung Diseases Cystic Fibrosis

Study Design

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Observational Model Type

FAMILY_BASED

Study Time Perspective

RETROSPECTIVE

Eligibility Criteria

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Inclusion Criteria

* Diagnosis of CF
Maximum Eligible Age

100 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role collaborator

Johns Hopkins University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Garry Cutting

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Locations

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Johns Hopkins University

Baltimore, Maryland, United States

Site Status

Countries

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United States

References

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McWilliams R, Hoover-Fong J, Hamosh A, Beck S, Beaty T, Cutting G. Problematic variation in local institutional review of a multicenter genetic epidemiology study. JAMA. 2003 Jul 16;290(3):360-6. doi: 10.1001/jama.290.3.360.

Reference Type BACKGROUND
PMID: 12865377 (View on PubMed)

Groman JD, Hefferon TW, Casals T, Bassas L, Estivill X, Des Georges M, Guittard C, Koudova M, Fallin MD, Nemeth K, Fekete G, Kadasi L, Friedman K, Schwarz M, Bombieri C, Pignatti PF, Kanavakis E, Tzetis M, Schwartz M, Novelli G, D'Apice MR, Sobczynska-Tomaszewska A, Bal J, Stuhrmann M, Macek M Jr, Claustres M, Cutting GR. Variation in a repeat sequence determines whether a common variant of the cystic fibrosis transmembrane conductance regulator gene is pathogenic or benign. Am J Hum Genet. 2004 Jan;74(1):176-9. doi: 10.1086/381001. Epub 2003 Dec 18.

Reference Type BACKGROUND
PMID: 14685937 (View on PubMed)

Boyle MP. Nonclassic cystic fibrosis and CFTR-related diseases. Curr Opin Pulm Med. 2003 Nov;9(6):498-503. doi: 10.1097/00063198-200311000-00009.

Reference Type BACKGROUND
PMID: 14534402 (View on PubMed)

Hefferon TW, Groman JD, Yurk CE, Cutting GR. A variable dinucleotide repeat in the CFTR gene contributes to phenotype diversity by forming RNA secondary structures that alter splicing. Proc Natl Acad Sci U S A. 2004 Mar 9;101(10):3504-9. doi: 10.1073/pnas.0400182101. Epub 2004 Mar 1.

Reference Type BACKGROUND
PMID: 14993601 (View on PubMed)

Other Identifiers

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R01HL068927

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1178

Identifier Type: -

Identifier Source: org_study_id

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