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Study Description

The major goal of this project is to apply second generation resequencing technology to identify disease causing variants influencing pediatric and adult lung diseases in a collection of two longitudinal population cohorts of cystic fibrosis patients that have been well characterized for a comprehensive set of clinical traits. In Phase I, exome sequencing was performed on 43 cystic fibrosis patients with early Pa infection and 48 cystic fibrosis patients with late Pa infection to identify variants influencing the time to onset of Pa infection. In Phase II, additional exomes were added to the study, to reach a total of 91 individuals with early Pa infection and 96 with late Pa infection. The majority of the 340 subjects of Phase II do not have a Pa infection phenotype, but instead have a pulmonary function phenotype (121 severe vs. 124 mild impairment) as determined by the survival corrected Kulich FEV percentile of Corey et al.. A small minority have intermediate phenotypes and/or show severe decline in lung function during childhood.

  • Study Weblink: NHLBI GO ESP Project
  • Study Types: Cohort, Exome Sequencing
  • Number of study subjects that have individual level data available through Authorized Access: 431

Authorized Access
Publicly Available Data (Public ftp)

Connect to the public download site. The site contains release notes and manifests. If available, the site also contains data dictionaries, variable summaries, documents, and truncated analyses.

Study Inclusion/Exclusion Criteria

Extreme phenotypes:

  • Youngest with Pa infection vs. oldest without Pa infection.
  • Very poor lung function vs. near normal lung function, adjusted for CFTR genotype.

Study History

Pseudomonas aeruginosa (Pa) is a ubiquitous environmental organism and the most significant pathogen in cystic fibrosis (CF) lung disease. Early Pa acquisition is a major concern for CF care providers given that chronic infection with this pathogen is associated with significant CF morbidity and mortality. Two longitudinal population cohorts of cystic fibrosis patients that have been well characterized for a comprehensive set of clinical traits for the study of Pa acquisition have contributed to this project. The first cohort, Early Pseudomonas Infection Control (CFES-CF1), the world's largest, multicenter, longitudinal, prospective cohort of early lung disease in young CF patients consists of 1,704 CF cases who were ages ≤ 12 years old with no prior isolation of Pa or at least a two-year history of Pa negative cultures. The second cohort, the NHLBI-GWAS to identify CF modifiers (CFES-CF2), consists of 1,208 patients who are at the extremes of lung disease severity.

Exome resequencing of phenotypic extremes represents a cost-effective and robust strategy for the sensitive and specific identification of variants causing protein-coding changes influencing risk for complex traits.

Selected publications
Diseases/Traits Related to Study (MESH terms)
Links to Related Resources
Authorized Data Access Requests
Study Attribution