Reverse Phenotyping Core

Study Overview
=================
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 gender. 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.

Detailed Description
-----------------
Study Design: RPC will be a data resource of genetic variants with the capability of performing phenotyping for selected study participants who have undergone genome or exome sequencing and were consented for data sharing and re-contact. De-identified genome or exome data will be collected as the RPC Genomic Data Archive and available in a web browser quantifying alleles in aggregate. Investigators may request additional data for research on the basis of variants of interest identified in the browser. Individuals with genetic variants of interest may be offered phenotyping under RPC. Phenotyping performed under RPC will include obtaining medical information, gathering biologic samples, and selected diagnostic studies that can be performed in the NIHCC (NIH Clinical Center). RPC will enable investigation of phenotypic consequences of genetic variation in humans by using a genomic ascertainment strategy to minimize the bias of phenotypic ascertainment. Primary Objective: To pilot the development of a cohort of individuals with genome or exome sequencing data who can be re-contacted for phenotyping and make those data available to and searchable by collaborators. To facilitate the completion of genotype-driven research projects by RPC or other investigators. Secondary Objectives: Secondary objectives will relate to the studies that will address phenotypic consequences of specific genetic variants identified in the RPC cohort. Such studies will include investigation of the phenotypic spectrum associated with genetic variation. Endpoints: This is a hypothesis-generating research study and therefore has no concrete endpoints.

Official Title
-----------------
Reverse Phenotyping Core (RPC)

Conditions
-----------------
Harboring of Unexpected Genetic Variant

Participation Criteria
=================
Eligibility Criteria
-----------------
INCLUSION CRITERIA: Participants in the RPC Genomic Data Archive must have exome or genome sequencing available that collaborators have permission to share for inclusion in our browser. 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.

Ages Eligible for Study
-----------------
Minimum Age: 4 Years
Maximum Age: 120 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Reverse Phenotyping Core<br>Individuals undergoing phenotyping by the Reverse Phenotyping Core (RPC) | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hypotheses from RPC to be tested | RPC will generate data regarding phenotypic consequences of genetic variants | yearly | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Resource, Variant, Sequencing, Genome, Phenotype, Natural History