Reverse Phenotyping Core

NCT03632239 | Enrolling By Invitation

• 2 other identifiers: 18012918-HG-0129
• Study Type: observational
• Target: 1,000
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Genes tell a person's body how to grow and work. All people have variations in their genes. Some of these cause differences that show up in a person's traits or their health, others do not. Researchers want to gather more data on people based on their genes. They want to use this data to learn more about diseases and possible treatments. Objectives: To develop a cohort of participants who can be contacted again for phenotyping and collect their genetic data. To share those data with other researchers and make them searchable. Eligibility: People already enrolled in a wide variety of protocols. They will be of varying health status, age, and sex. They will have had or plan to have exome or genome sequencing under their protocol. They can be re-contacted by the research team for possible other studies. Design: Participants will give basic details like contact and demographic information. Participants may answer questions about their personal health history, their family medical history, or their thoughts or reactions to data. Participants may have basic health tests. Their height, weight, or blood pressure may be checked. Participants may have tests of heart function. They may have an ultrasound or other non-invasive test. Participants may provide blood, urine, or other samples. Participants may have scans or other tests. Participants will get the results of all clinical tests in a letter. If any tests are abnormal, someone from the study will call the participant to explain what the results mean and what to do about them. Participants will get genetic testing results only if researchers think they could affect the health of the participant or their relatives.

Conditions

Harboring of Unexpected Genetic Variant

Keywords

Resource; Variant; Sequencing; Genome; Phenotype; Natural History

Outcome Measures

Primary Outcomes (1)

• Hypotheses from RPC to be tested

  RPC will generate data regarding phenotypic consequences of genetic variants

  yearly

Study Arms (1)

Reverse Phenotyping Core

Individuals undergoing phenotyping by the Reverse Phenotyping Core (RPC)

Eligibility Criteria

• Age: 4 Years - 120 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 undergone genome sequencing under separate protocol

You may qualify if:

• Participants in the RPC Genomic Data Archive must be re-contactable by the primary study team (e.g., the collaborator who contributes their data must be able to contact the participants).
• All participants must be \>= 4 years old.
• Health Perceptions Survey Criterion: Only adult participants who are able to provide consent for themselves will be eligible for this portion of the study.

Sponsors & Collaborators

• National Human Genome Research Institute (NHGRI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (5)

• Wilczewski CM, Obasohan J, Paschall JE, Zhang S, Singh S, Maxwell GL, Similuk M, Wolfsberg TG, Turner C, Biesecker LG, Katz AE. Genotype first: Clinical genomics research through a reverse phenotyping approach. Am J Hum Genet. 2023 Jan 5;110(1):3-12. doi: 10.1016/j.ajhg.2022.12.004.

  PMID: 36608682 BACKGROUND

• Garnai SJ, Brinkmeier ML, Emery B, Aleman TS, Pyle LC, Veleva-Rotse B, Sisk RA, Rozsa FW, Ozel AB, Li JZ, Moroi SE, Archer SM, Lin CM, Sheskey S, Wiinikka-Buesser L, Eadie J, Urquhart JE, Black GCM, Othman MI, Boehnke M, Sullivan SA, Skuta GL, Pawar HS, Katz AE, Huryn LA, Hufnagel RB; Genomic Ascertainment Cohort; Camper SA, Richards JE, Prasov L. Variants in myelin regulatory factor (MYRF) cause autosomal dominant and syndromic nanophthalmos in humans and retinal degeneration in mice. PLoS Genet. 2019 May 2;15(5):e1008130. doi: 10.1371/journal.pgen.1008130. eCollection 2019 May.

  PMID: 31048900 BACKGROUND

• Manthiram K, Preite S, Dedeoglu F, Demir S, Ozen S, Edwards KM, Lapidus S, Katz AE; Genomic Ascertainment Cohort; Feder HM Jr, Lawton M, Licameli GR, Wright PF, Le J, Barron KS, Ombrello AK, Barham B, Romeo T, Jones A, Srinivasalu H, Mudd PA, DeBiasi RL, Gul A, Marshall GS, Jones OY, Chandrasekharappa SC, Stepanovskiy Y, Ferguson PJ, Schwartzberg PL, Remmers EF, Kastner DL. Common genetic susceptibility loci link PFAPA syndrome, Behcet's disease, and recurrent aphthous stomatitis. Proc Natl Acad Sci U S A. 2020 Jun 23;117(25):14405-14411. doi: 10.1073/pnas.2002051117. Epub 2020 Jun 9.

  PMID: 32518111 BACKGROUND

• Johnston JJ, Brennan ML, Radenbaugh B, Yoo SJ, Hernandez SM; NHGRI Reverse Phenotyping Core; Lewis KL, Katz AE, Manolio TA, Biesecker LG. The ACMG SF v3.0 gene list increases returnable variant detection by 22% when compared with v2.0 in the ClinSeq cohort. Genet Med. 2022 Mar;24(3):736-743. doi: 10.1016/j.gim.2021.11.012. Epub 2021 Nov 18.

  PMID: 34906458 BACKGROUND

• Spontarelli K, Young VC, Sweazey R, Padro A, Lee J, Bueso T, Hernandez RM, Kim J, Katz A, Rossignol F, Turner C, Wilczewski CM, Maxwell GL, Holmgren M, Bailoo JD, Yano ST, Artigas P. ATP1A1-linked diseases require a malfunctioning protein product from one allele. Biochim Biophys Acta Mol Cell Res. 2024 Jan;1871(1):119572. doi: 10.1016/j.bbamcr.2023.119572. Epub 2023 Sep 1.

  PMID: 37659504 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

Study Officials

• Clesson E Turner, M.D.

  National Human Genome Research Institute (NHGRI)

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: August 14, 2018
• First Posted: August 15, 2018
• Study Start: January 23, 2020
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): December 29, 2028
• Last Updated: May 4, 2026

Record last verified: 2026-04-30

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Data in dbGap is stored per NIH policy. Data in the Reverse Phenotyping Core/TGAC browser will be stored for the remainder of the protocol (18-HG-0129) and the time the study is closed, a proposal to the IRB will be made to keep the data or destroy it.
• Access Criteria: dbGap is a controlled-access database with view-only access to summary-level information and individual-level genotype and sequence data associated with phenotypic features. The Reverse Phenotyping Core/TGAC browser allows researchers to identify particular genotypes or ranges of genotypes, while preserving the privacy of study participants by only displaying aggregate data for one or a limited number of loci in a search. The browser is located on NIH servers and searchable only by investigators in the NIH s intramural research program or external collaborators who have contributed sequence data.

Locations

US (1)