Seemingly HealthyPopSeqNCT04196374

Return of Genomic Results and Aggregate Penetrance in Population-Based Cohorts

A study testing Genomic Sequencing in people with Seemingly Healthy and Genetic Predisposition to Disease, run by Brigham and Women's Hospital at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 100 years
Conditions the study is for: Seemingly Healthy, Genetic Predisposition to Disease
What is being tested?: Genomic Sequencing
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 7,603 participants
Where: 2 sitesUnited States
Study dates: 9 Jun 2021to 30 May 2025
Phase: Interventional
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 100 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Living individuals enrolled in the Framingham Heart Study and the Jackson Heart Study who have had their genomes sequenced as part of the TOPMed program.
Adults over the age of 18 years
Those who have consented to have their DNA samples used for research purposes (and those who participate in gRoR who have consented to receive genomic information).

Who cannot join

Participants of the Framingham Heart Study or Jackson Heart Study who have not had their genomes sequenced as part of TOPMed
Participants who did not opt for genomic/genetic research
Participants who did/do not consent to receiving a genomic result (for the gRoR portion of this study only)

Trial locations and contacts

2 sites in 1 country.

United States2 sites

Framingham Heart Study
Framingham, Massachusetts, 01702
Jackson Heart Study
Jackson, Mississippi, 39213

Other trials in United States

About this study

The PopSeq Project is a prospective cohort study that will develop and implement a genomic return of results (gRoR) process in the Framingham Heart Study (FHS) and Jackson Heart Study (JHS) cohorts and explore associated medical, behavioral, and economic outcomes. The study will interpret the genomic sequences of JHS/FHS participants previously sequenced by TOPMed who have consented to genomic return of results and/or genetic testing. We will develop and apply new methods for scalable screening/ classification of genomic variants and will explore genomic penetrance by phenotyping a subset of participants in the FHS and JHS.

Read the detailed description

The objectives of this project are to: 1) Return clinically actionable genomic results to participants and track outcomes. Among living FHS/JHS participants who have consented to gRoR, we will contact those in whom a detrimental actionable variant is discovered in one of the genes noted on the ACMG recommended secondary findings list (estimate 2% of participants). 2) Improve high-throughput methods for identifying valid pathogenic variation. Refine and apply methods for high throughput screening of FHS/JHS genomes in a manner that retains high sensitivity for the detection of detrimental variants in ~3500 Mendelian disease-associated genes while reducing the false discovery rate of variants that are not pathogenic/likely pathogenic. 3) Explore aggregate penetrance for Mendelian diseases. Review phenotype data from a subset of FHS and JHS participants and compare this to genotypic data.

Data to be gathered include outcome and phenotypic data on the individuals who agree to gRoR and who learn that they have detrimental variant in one of the ACMG listed genes. These data will be self-reported through surveys and available medical records will be reviewed. Additional phenotypic data may be collected and reviewed for other non-actionable mendelian disease genes to explore genomic penetrance.

Research participants who are identified with a detrimental variant in an actionable gene may receive direct health benefits from learning this information; however, returning genomic results to healthy individuals not presenting for a medical indication may pose unexpected harms related to variant directed increases in screening and management. This study is focused on exploring the benefits and any potential harms related to returning genomic information in population-based cohorts. It will also allow us to better understand the penetrance of these variants in two populations not selected for disease status and will allow us to compare outcomes in a primarily African American population vs a Caucasian population. Developing methods to streamline variant analysis will help improve laboratory efficiency and will progress the field of variant curation and analysis.

Conditions: Seemingly Healthy, Genetic Predisposition to Disease
Being tested: Genomic Sequencing
Medical subject headings: Genetic Predisposition to Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Genomic SequencingGenetic
Whole Genome Sequencing and reporting of actionable genomic results for genes included on the ACMG secondary findings list.

Study groups in NCT04196374
Study group	Role	What they receive
FHS & JHS participants with an actionable genomic finding	Experimental	Framingham and Jackson Heart Study participants who have had their genomes sequenced as part of TOPMed will be notified if an actionable genetic result in an ACMG v2.0 gene is identified and will be offered the opportunity to have their research result clinically confirmed by the study. Receives: Genetic: Genomic Sequencing

What is being measured

The primary outcome is the main question the study is designed to answer.

Follow Through With Disclosure
Living JHS/FHS participants sequenced as part of the TOPMed program who were notified about an actionable genetic result that warranted having the research result verified who followed through with having their result confirmed and disclosed to their health care provider.
Measured: From genetic result notification to 8 months post-disclosure
Total Costs of Program Implementation
We will determine the costs and associated time demands of implementing gRoR using a microcosting approach in which study staff track the amount of time they spend and the resources they use for each step of the protocol. Ranges are based on 50% to 200% of point estimates given variability in wages and prices of services.
Measured: From the initiation of bioinformatics analysis to disclosure of confirmed actionable genetic finding (approximately 6 months).
Costs of Follow-Up Care
For follow-up medical care, we use a gross costing approach where we apply Centers for Medicare and Medicaid fee schedules to participant-reported referrals and tests.
Measured: 1 Year Post-Disclosure Survey (from 12 months to 15 months after disclosure of confirmed results)

Secondary outcomes (5)

Guideline Compliance
Number of participants with actionable genetic results who, per the judgement of a genetic specialist, had already met clinical criteria for genetic testing based on their personal and family histories of disease.
Measured: At the time of disclosure of confirmed findings (approximately 3 months after initial results notification)
New and Modified Diagnoses
We will examine cases to determine the percentage of individuals who report a new or modified diagnosis attributed to results disclosure.
Measured: 6 months Post-Disclosure Survey (6-9 months after disclosure of confirmed results);1 Year Post-Disclosure Survey (from 1 year to 15 months after disclosure of confirmed results)
Self-Rated Health
A single item of self rated health derived from the SF-12v2.
Measured: Post Disclosure Survey (up to 1 month from disclosure of confirmed results); 1 Year Post-Disclosure Survey (from 12 months to 15 months after disclosure of confirmed results)
Number of Participants With Recommendations to Referrals or Services During Clinical Disclosure Sessions
We reviewed chart notes from results disclosure sessions to determine whether referrals or services were recommended in response to genetic findings.
Measured: From disclosure to 1 month post-disclosure
Health Care Utilization
Health care utilization in response to results disclosure reported by participants in the one year follow-up survey, including referrals, tests and/or procedures, and changes to medications.
Measured: 1 year Post-Disclosure Survey (from 12 months to 15 months after disclosure of confirmed results)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

9 Jun 202130 May 2025

First posted12 Dec 2019
Study start9 Jun 2021
Primary completion30 May 2025
Study completion30 May 2025

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (18)Papers the sponsor has linked to this study.
Other trials for Seemingly HealthyStudies of the same condition, open and under way.
More trials run by Brigham and Women's HospitalThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Prevention
Allocation: Not applicable
Intervention model: Single group
Model description: Individuals who have had their DNA sequenced as part of TOPMed and are living will be notified if they have an actionable genomic result in an ACMG gene. There is no comparison group for this study.
Masking: None (open label)
Enrolment: 7,603 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04196374
Sponsor's protocol ID: R01HL143295
Acronym: PopSeq
Status last verified: Jul 2026
First submitted: 10 Dec 2019
Last updated: 3 Aug 2026
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No: Individual participant data will not be shared. Aggregate data will be shared through publication and will be considered upon request.

Publications

Biesecker LG, Green RC. Diagnostic clinical genome and exome sequencing. N Engl J Med. 2014 Sep 18;371(12):1170. doi: 10.1056/NEJMc1408914. No abstract available.
PubMed 25229935
Kalia SS, Adelman K, Bale SJ, Chung WK, Eng C, Evans JP, Herman GE, Hufnagel SB, Klein TE, Korf BR, McKelvey KD, Ormond KE, Richards CS, Vlangos CN, Watson M, Martin CL, Miller DT. Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics. Genet Med. 2017 Feb;19(2):249-255. doi: 10.1038/gim.2016.190. Epub 2016 Nov 17.
PubMed 27854360
Green RC, Berg JS, Grody WW, Kalia SS, Korf BR, Martin CL, McGuire AL, Nussbaum RL, O'Daniel JM, Ormond KE, Rehm HL, Watson MS, Williams MS, Biesecker LG; American College of Medical Genetics and Genomics. ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing. Genet Med. 2013 Jul;15(7):565-74. doi: 10.1038/gim.2013.73. Epub 2013 Jun 20.
PubMed 23788249
Wolf SM, Lawrenz FP, Nelson CA, Kahn JP, Cho MK, Clayton EW, Fletcher JG, Georgieff MK, Hammerschmidt D, Hudson K, Illes J, Kapur V, Keane MA, Koenig BA, Leroy BS, McFarland EG, Paradise J, Parker LS, Terry SF, Van Ness B, Wilfond BS. Managing incidental findings in human subjects research: analysis and recommendations. J Law Med Ethics. 2008 Summer;36(2):219-48, 211. doi: 10.1111/j.1748-720X.2008.00266.x.
PubMed 18547191
Wolf SM, Crock BN, Van Ness B, Lawrenz F, Kahn JP, Beskow LM, Cho MK, Christman MF, Green RC, Hall R, Illes J, Keane M, Knoppers BM, Koenig BA, Kohane IS, Leroy B, Maschke KJ, McGeveran W, Ossorio P, Parker LS, Petersen GM, Richardson HS, Scott JA, Terry SF, Wilfond BS, Wolf WA. Managing incidental findings and research results in genomic research involving biobanks and archived data sets. Genet Med. 2012 Apr;14(4):361-84. doi: 10.1038/gim.2012.23.
PubMed 22436882
Burke W, Evans BJ, Jarvik GP. Return of results: ethical and legal distinctions between research and clinical care. Am J Med Genet C Semin Med Genet. 2014 Mar;166C(1):105-11. doi: 10.1002/ajmg.c.31393. Epub 2014 Mar 10.
PubMed 24616381
National Heart, Lung, and Blood Institute working group; Fabsitz RR, McGuire A, Sharp RR, Puggal M, Beskow LM, Biesecker LG, Bookman E, Burke W, Burchard EG, Church G, Clayton EW, Eckfeldt JH, Fernandez CV, Fisher R, Fullerton SM, Gabriel S, Gachupin F, James C, Jarvik GP, Kittles R, Leib JR, O'Donnell C, O'Rourke PP, Rodriguez LL, Schully SD, Shuldiner AR, Sze RK, Thakuria JV, Wolf SM, Burke GL. Ethical and practical guidelines for reporting genetic research results to study participants: updated guidelines from a National Heart, Lung, and Blood Institute working group. Circ Cardiovasc Genet. 2010 Dec;3(6):574-80. doi: 10.1161/CIRCGENETICS.110.958827.
PubMed 21156933
Natarajan P, Gold NB, Bick AG, McLaughlin H, Kraft P, Rehm HL, Peloso GM, Wilson JG, Correa A, Seidman JG, Seidman CE, Kathiresan S, Green RC. Aggregate penetrance of genomic variants for actionable disorders in European and African Americans. Sci Transl Med. 2016 Nov 9;8(364):364ra151. doi: 10.1126/scitranslmed.aag2367.
PubMed 27831900
Christensen KD, Phillips KA, Green RC, Dukhovny D. Cost Analyses of Genomic Sequencing: Lessons Learned from the MedSeq Project. Value Health. 2018 Sep;21(9):1054-1061. doi: 10.1016/j.jval.2018.06.013. Epub 2018 Aug 14.
PubMed 30224109
Christensen KD, Vassy JL, Phillips KA, Blout CL, Azzariti DR, Lu CY, Robinson JO, Lee K, Douglas MP, Yeh JM, Machini K, Stout NK, Rehm HL, McGuire AL, Green RC, Dukhovny D; MedSeq Project. Short-term costs of integrating whole-genome sequencing into primary care and cardiology settings: a pilot randomized trial. Genet Med. 2018 Dec;20(12):1544-1553. doi: 10.1038/gim.2018.35. Epub 2018 Mar 22.
PubMed 29565423
Roberts JS, Robinson JO, Diamond PM, Bharadwaj A, Christensen KD, Lee KB, Green RC, McGuire AL; MedSeq Project team. Patient understanding of, satisfaction with, and perceived utility of whole-genome sequencing: findings from the MedSeq Project. Genet Med. 2018 Sep;20(9):1069-1076. doi: 10.1038/gim.2017.223. Epub 2018 Jan 4.
PubMed 29300387
Vassy JL, Christensen KD, Schonman EF, Blout CL, Robinson JO, Krier JB, Diamond PM, Lebo M, Machini K, Azzariti DR, Dukhovny D, Bates DW, MacRae CA, Murray MF, Rehm HL, McGuire AL, Green RC; MedSeq Project. The Impact of Whole-Genome Sequencing on the Primary Care and Outcomes of Healthy Adult Patients: A Pilot Randomized Trial. Ann Intern Med. 2017 Jun 27;167(3):159-169. doi: 10.7326/M17-0188. Print 2017 Aug 1.
PubMed 28654958
Christensen KD, Dukhovny D, Siebert U, Green RC. Assessing the Costs and Cost-Effectiveness of Genomic Sequencing. J Pers Med. 2015 Dec 10;5(4):470-86. doi: 10.3390/jpm5040470.
PubMed 26690481
Lupo PJ, Robinson JO, Diamond PM, Jamal L, Danysh HE, Blumenthal-Barby J, Lehmann LS, Vassy JL, Christensen KD, Green RC, McGuire AL; MedSeq Project team. Patients' perceived utility of whole-genome sequencing for their healthcare: findings from the MedSeq project. Per Med. 2016 Jan 1;13(1):13-20. doi: 10.2217/pme.15.45. Epub 2016 Jan 8.
PubMed 27019659
Wolf SM, Branum R, Koenig BA, Petersen GM, Berry SA, Beskow LM, Daly MB, Fernandez CV, Green RC, LeRoy BS, Lindor NM, O'Rourke PP, Breitkopf CR, Rothstein MA, Van Ness B, Wilfond BS. Returning a Research Participant's Genomic Results to Relatives: Analysis and Recommendations. J Law Med Ethics. 2015 Fall;43(3):440-63. doi: 10.1111/jlme.12288.
PubMed 26479555

Study at a glance

From the registry record, last updated by the sponsor on 3 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Return of Genomic Results and Aggregate Penetrance in Population-Based Cohorts
ClinicalTrials.gov ID: NCT04196374
Acronym / sponsor ID: PopSeq / R01HL143295
Conditions: Seemingly Healthy, Genetic Predisposition to Disease
Study type: Interventional
Recruitment status: Completed
Enrolment: 7,603 participants (actual)
Lead sponsor: Brigham and Women's HospitalUniversity, hospital or other
Collaborators: Framingham Heart Study, Jackson Heart Study, Broad Institute of MIT and Harvard, University of Mississippi Medical Center, Boston University, Partners HealthCare
Study start: 9 Jun 2021 (actual)
Primary completion: 30 May 2025 (actual)
Study completion: 30 May 2025 (actual)
First posted: 12 Dec 2019 (actual)
Results: Posted 3 Aug 2026

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Prevention
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1
Model description: Individuals who have had their DNA sequenced as part of TOPMed and are living will be notified if they have an actionable genomic result in an ACMG gene. There is no comparison group for this study.

Arm	Type	Receives
FHS & JHS participants with an actionable genomic finding	Experimental	Genetic: Genomic SequencingFramingham and Jackson Heart Study participants who have had their genomes sequenced as part of TOPMed will be notified if an actionable genetic result in an ACMG v2.0 gene is identified and will be offered the opportunity to have their research result clinically confirmed by the study.

Who may qualify

Ages: 18 to 100 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

Living individuals enrolled in the Framingham Heart Study and the Jackson Heart Study who have had their genomes sequenced as part of the TOPMed program.
Adults over the age of 18 years
Those who have consented to have their DNA samples used for research purposes (and those who participate in gRoR who have consented to receive genomic information).

Key exclusion criteria (3 listed)

Participants of the Framingham Heart Study or Jackson Heart Study who have not had their genomes sequenced as part of TOPMed
Participants who did not opt for genomic/genetic research
Participants who did/do not consent to receiving a genomic result (for the gRoR portion of this study only)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Genomic SequencingWhole Genome Sequencing and reporting of actionable genomic results for genes included on the ACMG secondary findings list.	Genetic	FHS & JHS participants with an actionable genomic finding

Primary outcome

Follow Through With Disclosure
Time frame: From genetic result notification to 8 months post-disclosure
Living JHS/FHS participants sequenced as part of the TOPMed program who were notified about an actionable genetic result that warranted having the research result verified who followed through with having their result confirmed and disclosed to their health care provider.
Total Costs of Program Implementation
Time frame: From the initiation of bioinformatics analysis to disclosure of confirmed actionable genetic finding (approximately 6 months).
We will determine the costs and associated time demands of implementing gRoR using a microcosting approach in which study staff track the amount of time they spend and the resources they use for each step of the protocol. Ranges are based on 50% to 200% of point estimates given variability in wages and prices of services.
Costs of Follow-Up Care
Time frame: 1 Year Post-Disclosure Survey (from 12 months to 15 months after disclosure of confirmed results)
For follow-up medical care, we use a gross costing approach where we apply Centers for Medicare and Medicaid fee schedules to participant-reported referrals and tests.

5 secondary outcomes

Guideline Compliance
Time frame: At the time of disclosure of confirmed findings (approximately 3 months after initial results notification)
New and Modified Diagnoses
Time frame: 6 months Post-Disclosure Survey (6-9 months after disclosure of confirmed results);1 Year Post-Disclosure Survey (from 1 year to 15 months after disclosure of confirmed results)
Self-Rated Health
Time frame: Post Disclosure Survey (up to 1 month from disclosure of confirmed results); 1 Year Post-Disclosure Survey (from 12 months to 15 months after disclosure of confirmed results)
Number of Participants With Recommendations to Referrals or Services During Clinical Disclosure Sessions
Time frame: From disclosure to 1 month post-disclosure
Health Care Utilization
Time frame: 1 year Post-Disclosure Survey (from 12 months to 15 months after disclosure of confirmed results)

Results and safety

Results posted to the registry on 3 Aug 2026, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
FHS & JHS Participants With an Actionable Genomic Finding	7,603	48

Primary outcome: Follow Through With Disclosure

Time frame: From genetic result notification to 8 months post-disclosure. Count of participants. Unit: Participants

Measure	FHS & JHS Participants With an Actionable Genomic Finding n = 71
Value	48

Population analysed: Living JHS/FHS participants sequenced as part of the TOPMed program who were notified about an actionable genetic result that warranted having the research result verified.

Primary outcome: Total Costs of Program Implementation

Time frame: From the initiation of bioinformatics analysis to disclosure of confirmed actionable genetic finding (approximately 6 months).. Mean (Full Range). Unit: 2025 U.S. Dollars

Measure	FHS & JHS Participants With an Actionable Genomic Finding n = 7603
Value	39568 (19784 to 79136)

Population analysed: Implementation costs included the effort and resources needed to screen the existing genetic data for 7,603 FHS and JHS participants for actionable genetic findings.

Primary outcome: Costs of Follow-Up Care

Time frame: 1 Year Post-Disclosure Survey (from 12 months to 15 months after disclosure of confirmed results). Mean (Full Range). Unit: 2025 U.S. Dollars

Measure	FHS & JHS Participants With an Actionable Genomic Finding n = 25
Value	517 (0 to 4285)

Population analysed: Participants with confirmed and disclosed actionable genetic findings who completed the 12 month follow up survey.

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: From initial contact about a possible genomic finding until the end of follow-up (approximately 15 months after initial notification). Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
FHS & JHS Participants With an Actionable Genomic Finding	0 of 71 (0%)	2 of 71 (2.8%)	0 of 71

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2026.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 25229935Biesecker LG, Green RC. Diagnostic clinical genome and exome sequencing. N Engl J Med. 2014 Sep 18;371(12):1170. doi: 10.1056/NEJMc1408914. No abstract available.
Background: PubMed 27854360Kalia SS, Adelman K, Bale SJ, Chung WK, Eng C, Evans JP, Herman GE, Hufnagel SB, Klein TE, Korf BR, McKelvey KD, Ormond KE, Richards CS, Vlangos CN, Watson M, Martin CL, Miller DT. Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics. Genet Med. 2017 Feb;19(2):249-255. doi: 10.1038/gim.2016.190. Epub 2016 Nov 17.
Background: PubMed 23788249Green RC, Berg JS, Grody WW, Kalia SS, Korf BR, Martin CL, McGuire AL, Nussbaum RL, O'Daniel JM, Ormond KE, Rehm HL, Watson MS, Williams MS, Biesecker LG; American College of Medical Genetics and Genomics. ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing. Genet Med. 2013 Jul;15(7):565-74. doi: 10.1038/gim.2013.73. Epub 2013 Jun 20.
Background: PubMed 18547191Wolf SM, Lawrenz FP, Nelson CA, Kahn JP, Cho MK, Clayton EW, Fletcher JG, Georgieff MK, Hammerschmidt D, Hudson K, Illes J, Kapur V, Keane MA, Koenig BA, Leroy BS, McFarland EG, Paradise J, Parker LS, Terry SF, Van Ness B, Wilfond BS. Managing incidental findings in human subjects research: analysis and recommendations. J Law Med Ethics. 2008 Summer;36(2):219-48, 211. doi: 10.1111/j.1748-720X.2008.00266.x.
Background: PubMed 22436882Wolf SM, Crock BN, Van Ness B, Lawrenz F, Kahn JP, Beskow LM, Cho MK, Christman MF, Green RC, Hall R, Illes J, Keane M, Knoppers BM, Koenig BA, Kohane IS, Leroy B, Maschke KJ, McGeveran W, Ossorio P, Parker LS, Petersen GM, Richardson HS, Scott JA, Terry SF, Wilfond BS, Wolf WA. Managing incidental findings and research results in genomic research involving biobanks and archived data sets. Genet Med. 2012 Apr;14(4):361-84. doi: 10.1038/gim.2012.23.
Background: PubMed 24616381Burke W, Evans BJ, Jarvik GP. Return of results: ethical and legal distinctions between research and clinical care. Am J Med Genet C Semin Med Genet. 2014 Mar;166C(1):105-11. doi: 10.1002/ajmg.c.31393. Epub 2014 Mar 10.
Background: PubMed 21156933National Heart, Lung, and Blood Institute working group; Fabsitz RR, McGuire A, Sharp RR, Puggal M, Beskow LM, Biesecker LG, Bookman E, Burke W, Burchard EG, Church G, Clayton EW, Eckfeldt JH, Fernandez CV, Fisher R, Fullerton SM, Gabriel S, Gachupin F, James C, Jarvik GP, Kittles R, Leib JR, O'Donnell C, O'Rourke PP, Rodriguez LL, Schully SD, Shuldiner AR, Sze RK, Thakuria JV, Wolf SM, Burke GL. Ethical and practical guidelines for reporting genetic research results to study participants: updated guidelines from a National Heart, Lung, and Blood Institute working group. Circ Cardiovasc Genet. 2010 Dec;3(6):574-80. doi: 10.1161/CIRCGENETICS.110.958827.
Background: PubMed 27831900Natarajan P, Gold NB, Bick AG, McLaughlin H, Kraft P, Rehm HL, Peloso GM, Wilson JG, Correa A, Seidman JG, Seidman CE, Kathiresan S, Green RC. Aggregate penetrance of genomic variants for actionable disorders in European and African Americans. Sci Transl Med. 2016 Nov 9;8(364):364ra151. doi: 10.1126/scitranslmed.aag2367.
Background: PubMed 30224109Christensen KD, Phillips KA, Green RC, Dukhovny D. Cost Analyses of Genomic Sequencing: Lessons Learned from the MedSeq Project. Value Health. 2018 Sep;21(9):1054-1061. doi: 10.1016/j.jval.2018.06.013. Epub 2018 Aug 14.
Background: PubMed 29565423Christensen KD, Vassy JL, Phillips KA, Blout CL, Azzariti DR, Lu CY, Robinson JO, Lee K, Douglas MP, Yeh JM, Machini K, Stout NK, Rehm HL, McGuire AL, Green RC, Dukhovny D; MedSeq Project. Short-term costs of integrating whole-genome sequencing into primary care and cardiology settings: a pilot randomized trial. Genet Med. 2018 Dec;20(12):1544-1553. doi: 10.1038/gim.2018.35. Epub 2018 Mar 22.
Background: PubMed 29300387Roberts JS, Robinson JO, Diamond PM, Bharadwaj A, Christensen KD, Lee KB, Green RC, McGuire AL; MedSeq Project team. Patient understanding of, satisfaction with, and perceived utility of whole-genome sequencing: findings from the MedSeq Project. Genet Med. 2018 Sep;20(9):1069-1076. doi: 10.1038/gim.2017.223. Epub 2018 Jan 4.
Background: PubMed 28654958Vassy JL, Christensen KD, Schonman EF, Blout CL, Robinson JO, Krier JB, Diamond PM, Lebo M, Machini K, Azzariti DR, Dukhovny D, Bates DW, MacRae CA, Murray MF, Rehm HL, McGuire AL, Green RC; MedSeq Project. The Impact of Whole-Genome Sequencing on the Primary Care and Outcomes of Healthy Adult Patients: A Pilot Randomized Trial. Ann Intern Med. 2017 Jun 27;167(3):159-169. doi: 10.7326/M17-0188. Print 2017 Aug 1.
Individual participant dataSharing planned: No. Individual participant data will not be shared. Aggregate data will be shared through publication and will be considered upon request.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing Genomic Sequencing in people with Seemingly Healthy and Genetic Predisposition to Disease, run by Brigham and Women's Hospital at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 3 Aug 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Follow Through With Disclosure (time frame: From genetic result notification to 8 months post-disclosure). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04196374, which also lists 18 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Aug 2026.