UW ISeqU: Clinical Impact of Whole-genome Sequencing in Adults
Trial Snapshot
- Phase
- Not Applicable
- Status
- Enrolling By Invitation
- Sponsor
- University of Washington
- Enrollment
- 1,000
- Locations
- 1
- Primary Endpoint
- Diagnostic Yield of Clinical Genome Sequencing
Study Overview
Brief Summary
The goal of this study is to learn how clinical whole genome sequencing can help identify diagnoses and guide medical care in adults. The study is based on the hypothesis that genome sequencing will identify a genetic explanation in some adults whose condition has not previously been diagnosed and that some results will change medical care. The main questions it aims to answer are:
- How often does genome sequencing identify a genetic diagnosis that explains or contributes to a participant's symptoms?
- How do genetic results affect medical care and decision-making?
- Is genome sequencing feasible and acceptable to adult patients and families?
- Are there differences in access to genetic testing or diagnosis across different groups of patients?
Participants will:
- Provide a blood sample (often collected during routine care) or cheek swab for genetic testing
- Allow researchers to review their medical records
- Receive genetic results that will also be shared with their medical team
- May be asked to complete a brief survey or interview about their experience
Researchers will follow participants over time to understand how genetic testing impacts diagnosis and care.
Detailed Description
This is a prospective observational cohort study evaluating the use of clinical whole genome sequencing in adults with unexplained medical conditions, atypical disease courses, or clinical presentations for which a genetic contribution is suspected. Participants will be identified at the University of Washington Medicine sites (UW Montlake and Harborview Medical Center). The study is intended to characterize how genome sequencing can be incorporated into adult clinical care. Participation is voluntary and does not replace standard diagnostic evaluation or treatment.
Potential participants will be identified through review of hospital admissions and referrals from treating clinicians or specialty services. Informed consent may be completed in person, by telephone, or by secure videoconference. When a hospitalized participant is unable to provide consent because of illness or impaired decision-making capacity, consent may be obtained from a legally authorized representative in accordance with applicable requirements. During consent, participants will indicate whether they wish to receive ACMG medically actionable secondary findings and whether they agree to future contact.
After enrollment, the study team will collect clinical and phenotypic information relevant to genomic interpretation. Information may include the participant's presenting symptoms, medical and family history, prior diagnostic testing, medications, hospital course, and subsequent clinical care. Data will be obtained from participant or family interview, review of the electronic health record, and communication with the treating team. Clinical information from before and after sequencing will be collected to support interpretation and to evaluate the downstream effects of genomic findings.
The only physical procedure is collection of a biospecimen for genomic testing. Research blood collection will be coordinated with a clinically indicated blood draw to avoid an additional venipuncture. Alternatively, a buccal swab may be used.
A close biological relative may also be enrolled as a genetic comparator when this would assist in genetic interpretation. Comparator participation is optional. Comparators will provide a buccal specimen and limited identifying information needed for laboratory testing. Their medical records will not be reviewed.
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Prospective
Eligibility Criteria
- Ages
- 18 Years to 50 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Person has a medical condition that does not yet have a clear explanation
- •Enough medical information is available within the UW Medicine system to evaluate the person's condition and interpret genetic test results
- •A blood sample or cheek-swab sample can be collected for genetic testing
- •The person does not already have a confirmed genetic diagnosis that fully explains their current medical condition
- •The person, or their legally authorized representative when applicable, is willing and able to provide informed consent.
Exclusion Criteria
- •The current illness has a clear non-genetic explanation, such as a traumatic injury, confirmed overdose or intoxication, or an infection that fully explains the illness
- •The person previously had genetic testing specifically for the current condition or symptoms, including prior whole-exome or whole-genome sequencing
- •The person is currently incarcerated.
- •The person has had a donor stem cell, bone marrow transplant or active blood cancer that makes a sample unsuitable for testing their inherited genetic information
Outcomes
Primary Outcomes
Diagnostic Yield of Clinical Genome Sequencing
Time Frame: Through study completion, an average of 3 years
Number and percentage of participants with one or more definitive or possible diagnostic findings on clinical genome sequencing. This will be further stratified as secondary outcome measures by clinical and demographic characteristics.
Secondary Outcomes
- Short-term and long-term changes in medical management(At 6 months after testing and at 3 years after testing)
Investigators
Evonne McArthur
Fellow Physician
University of Washington