CF Foundation Whole Genome Sequencing Project as a Research Tool

The Cystic Fibrosis Foundation launched the Cystic Fibrosis Whole Genome Sequencing (WGS) Project 2018 with the goal of using DNA sequencing and analysis techniques to correlate changes in the DNA sequence with confidential medical histories of more than 5,000 people with CF. This project created a unique and rich dataset, combining genome sequences with clinical data from the CF Foundation Patient Registry, that can be used to investigate differences in DNA that may explain how CF and complications of CF develop differently in different people -- even those who have the same CFTR mutations. Identifying genes in addition to CFTR that play a role in CF not only provides us with useful information about the potential progression of the disease in different people with CF, but may also identify potential new targets (the proteins generated by these genes) for possible treatments.

The WGS Project consists of confidential data from individuals who participated in the Early Pseudomonas Infection Control (EPIC), Extremes of Phenotype, and Twin/Sibs Patient studies: 

• The EPIC Observational Study: Longitudinal Assessment of Risk Factors for and Impact of Pseudomonas aeruginosa Acquisition and Early Anti-Pseudomonal Treatment in Children with CF
• Genetic Modifiers of CF: Sibling Study
• Genetic Modifiers in Cystic Fibrosis Lung Disease

A list of ongoing and completed WGS data requests will be updated quarterly. We encourage investigators to review these projects to foster collaboration and prevent duplication of efforts.

Requesting Data

Academic investigators who wish to request WGS data for the purpose of pursuing a new research question must complete and submit a formal application through our electronic submission platform, which includes:

• Signed confidentiality agreement (last page of application guidance)
• Research proposal
• IRB approval (can be pending at the time of submission but must be approved to receive data)
• List of the variables requested 
• Format of WGS data requested 
  • BAM files
  • Variant call format (VCF) files  

Note: Investigators wishing to perform validation studies on published datasets from previous WGS approved projects should submit a written request to WGSrequests@cff.org describing the data being requested and the analysis to be completed. 

Investigators from Industry who wish to request WGS data should contact WGSrequests@cff.org. 

The formal application guidance document indicates the format of the applications, regulatory requirements, and other responsibilities for individuals receiving WGS data. We encourage involvement of a CF Foundation-accredited care center director or care team member as a member of the project team. 

Meeting these requirements allows the CF Foundation to maintain our obligation and commitment to protecting the privacy of people with CF who allow their information to be included in the Registry and the privacy of people with CF who participated in the EPIC, Extremes of Phenotype, and Twin/Sibs studies. This information is protected by the Health Insurance Portability and Accountability Act (HIPAA) and the informed consent that was signed by every Registry, EPIC, Extremes of Phenotype, or Twin/Sibs participant or their legal guardian through their CF Foundation-accredited care center. The CF Foundation is entrusted with this information and is responsible for keeping that information private and secure. For this reason, we have a standard set of criteria that must be met by all individuals requesting to use this data.

The Approval Process

Requests for WGS data undergo a thorough review for scientific merit and to ensure that the information needed for the study is available, and to assess the proposed study design feasibility, and likelihood that analyses will yield valid and meaningful results. This review is completed by members of the Patient Registry/Comparative Effectiveness Research Committee, comprised of CF clinicians and researchers working with CF Foundation staff, and external reviewers who are versed in conducting genetic studies and bioinformatic/data analysis to evaluate the research proposal design and analytic approaches proposed in the study.

The request and review process can take at least three months once the application and variable list are submitted. If the application is approved, that applicant will be sent an Information Use Agreement (IUA) that will need to be signed by the requesting institution (this process may take weeks to months depending on the processing time at the institution).  Once all regulatory and legal requirements are met, data will be securely delivered to the researcher. 

Study investigators are required to submit annual progress reports for projects extending beyond one-year in length and a final report once their analysis has been completed. Investigators are encouraged to present their findings to the larger CF community at the annual North American Cystic Fibrosis Conference and through dissemination in peer-reviewed journals. Please note the CF Foundation requires that all conference abstracts and manuscripts are sent to the CF Foundation for review prior to submission to ensure compliance with our terms and conditions.  

Questions? Please contact us at WGSrequests@cff.org.