Genetic Modifiers of Cystic Fibrosis: Sibling Study

Completed

• Conditions: Cystic Fibrosis; Lung Diseases

• Registration Number: NCT00037778
• Lead Sponsor: Johns Hopkins University

Brief Summary

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

Detailed Description

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.

Study Timeline

• Study Start: 2001-09
• Study First Submitted: 2002-05-20
• Study First Submitted QC: 2002-05-20
• Study First Posted: 2002-05-21
• Primary Completion: 2013-02
• Study Completion: 2013-02
• Status Verified: 2016-08
• Last Update Submitted: 2016-08-29
• Last Update Posted: 2016-08-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 3459

Inclusion Criteria

• Diagnosis of CF

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Variation among genes in siblings with cystic fibrosis as assessed by DNA	Single collection

Trial Locations

Locations (1)

Johns Hopkins University; 🇺🇸 Baltimore, Maryland, United States