Genomic Services Research Program

NCT02595957 | Recruiting

• 2 other identifiers: 16001716-HG-0017
• Study Type: observational
• Target: 5,000
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Genes are the instructions a person s body uses to function. Genome sequencing reads through all of a person s genes. Everyone has many gene variants, and most do not cause disease. Some gene variants called secondary findings may be important for a person s health even if they are not related to the reason why a person had genome sequencing done. Researchers want to learn more about what it means to have a secondary finding. Objectives: To learn about how gene variants may affect a person s health. To learn about how people understand their genetic test results. Eligibility: People with secondary findings from genetic testing done as part of a research study, clinical care, or other methods. Design: Participants may be asked to do an online survey and phone interview to ask what they think about their results, their healthcare, and if they talk with their family about the result. Eligible participants may be offered a visit to the NIH Clinical Center where they will be evaluated for health problems related to the secondary finding. DNA samples that were already collected may be studied. Participants may be asked to send in a second DNA sample (blood or saliva). These will be used to verify any findings. Participants who have a secondary finding can get genetic counseling.

Conditions

Colon Cancer; Breast Cancer

Keywords

Genome Sequencing; Secondary Findings; Return of Results; Natural History; Exome Sequencing

Outcome Measures

Primary Outcomes (4)

• Health impacts of SF receipt

  We will assess the health impacts of SF receipt and healthcare processes affecting outcomes in SF recipients.

  enrollment and return of results

• Adherence to medical recommendations

  We will assess what individual, community, and systemic factors influence recipients' follow through on recommendations and how they communicate SF results with family members.

  enrollment and return of results

• Family based positive predictive value

  We will assess penetrance using the family-based positive predictive value metric

  return of results and cascade testing

• Responses and perceptions

  We will assess affective responses and healthcare and behavioral changes to receiving positive SF results

  enrollment and return of results

Study Arms (2)

Cascade Testing

Family members of individuals who have received secondary genomic findings after exome/genome sequencing

Secondary findings recipients

Individuals who have received secondary genomic findings after exome/genome sequencing

Eligibility Criteria

• Age: 1 Month - 105 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Individuals who have participated in a sequencing study at the NIH or elsewhere who have have received secondary findings through other means are eligible.

* ELIGIBILITY CRITERIA: We employ a referral form through SurveyMonkey to receive referrals from recruitment partners or self-referrals. This serves as an intake form and self-reported eligibility review. This form asks for contact information, key information about the prospective participant s SF, and subjective understanding of their result. If we conclude, based on a review of the SF and available personal and/or family history, that the pathogenicity of the SF is not at least likely pathogenic, that participant may be eligible for the survey, interview, and/or re-contact for future follow-up, but will not complete any other protocol procedures (such as cascade testing). If a participant is consented and information arises during the social and behavioral study procedures that lead study staff to believe the genetic result does not qualify as an SF, the participant will be considered a screen failure and will not continue with study procedures. We plan to offer enrollment in this protocol to English- or Spanish-speaking recipients of SF. We do not have trained staff who can conduct the interviews in languages other than English and Spanish. If a caregiver of a minor or adult who is unable to consent is enrolled as an index participant to complete the survey and interview on behalf of the SF recipient, they may also be eligible for cascade testing to relate presence of an SF-related phenotype in a family member with presence or absence of SF genotype. -We may enroll a child in this protocol if he/she is the only person in his/her family who has the SF, is symptomatic of the disease, or is in the age range to receive screening for the disease (e.g., Wilson disease and familial hypercholesterolemia have childhood onset). We will not enroll neonates (less than one month old). * We may enroll adults who are unable to consent (i.e., an individual who is impaired at the time of consent) in this protocol if he/she is the only person in his/her family who has the SF, is symptomatic of the disease, or is in the age range to receive screening for the disease. * We may enroll women who are pregnant in this protocol and women who become pregnant during the study can continue their participation. We will not perform prenatal genetic testing. * NIH staff members are not prohibited from enrollment if they meet the study s eligibility criteria. The study team will make every effort to protect the confidentiality of the NIH staff member s health information, to minimize any pressure on or discomfort of the NIH staff member and provide a copy of the NIH Frequently Asked Questions (FAQs) for Staff Who are Considering Participation in NIH Research , before consent is obtained.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• National Human Genome Research Institute (NHGRI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Publications (1)

• Sapp JC, Johnston JJ, Driscoll K, Heidlebaugh AR, Miren Sagardia A, Dogbe DN, Umstead KL, Turbitt E, Alevizos I, Baron J, Bonnemann C, Brooks B, Donkervoort S, Jee YH, Linehan WM, McMahon FJ, Moss J, Mullikin JC, Nielsen D, Pelayo E, Remaley AT, Siegel R, Su H, Zarate C; NISC Comparative Sequencing Program; Manolio TA, Biesecker BB, Biesecker LG. Evaluation of Recipients of Positive and Negative Secondary Findings Evaluations in a Hybrid CLIA-Research Sequencing Pilot. Am J Hum Genet. 2018 Sep 6;103(3):358-366. doi: 10.1016/j.ajhg.2018.07.018. Epub 2018 Aug 16.

  PMID: 30122538 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Colonic Neoplasms; Breast Neoplasms

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Leslie G Biesecker, M.D.

  National Human Genome Research Institute (NHGRI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Julie C Sapp

CONTACT

(301) 435-2832; sappj@mail.nih.gov

Leslie G Biesecker, M.D.

CONTACT

(301) 402-2041; lesb@mail.nih.gov

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 2015
• First Posted: November 4, 2015
• Study Start: September 16, 2014
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: May 7, 2026

Record last verified: 2026-04-24

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)