Genomic Sequencing for Genetic Predisposition

(PopSeq Trial)

No longer recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Brigham and Women's Hospital

Disqualifiers: Unsequenced genomes, No genomic consent, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how sharing genetic information affects health, behavior, and finances. It involves participants from the Framingham and Jackson Heart Studies who have already had their DNA sequenced. The trial informs participants of any significant genetic findings and offers a chance to confirm these clinically. It suits those who have agreed to use their DNA for research and wish to receive their genetic results. As an unphased trial, it provides a unique opportunity to explore personal genetic insights and their impact on life.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What prior data suggests that genomic sequencing is safe?

Research has shown that genomic sequencing, such as whole genome sequencing (WGS) and whole exome sequencing (WES), is generally manageable for individuals. These methods are widely used in healthcare to understand genetic differences and help diagnose rare diseases by examining a person's entire genetic code or specific parts related to their condition.

Studies have found these sequencing methods to be safe. They involve analyzing DNA, the molecule that carries genetic information, and do not require invasive procedures. Participants typically provide a saliva or blood sample for this analysis.

The main concern with genomic sequencing involves privacy and the potential emotional impact of learning about genetic risks. However, regarding physical safety, no significant negative effects have been reported. This makes genomic sequencing a low-risk option for those considering joining a study like the PopSeq Project. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about genomic sequencing for genetic predisposition because it offers a personalized approach to identifying potential health risks. Unlike traditional methods that rely on family history or symptom-based diagnosis, genomic sequencing can pinpoint specific genetic variants that may predispose individuals to certain conditions. This method empowers individuals with actionable information, allowing for earlier interventions or lifestyle adjustments to mitigate potential health issues. By focusing on the actual genetic makeup, this approach can lead to more precise and tailored healthcare strategies, potentially improving outcomes and prevention measures.

What evidence suggests that genomic sequencing is effective for identifying genetic predispositions?

Research shows that studying genes can help determine the likelihood of developing certain diseases. For example, new technology allows scientists to quickly read large sections of DNA, making it easier to identify genes that might cause health problems. Studies have found that examining the entire set of genes is particularly useful for diagnosing rare and unknown diseases. This approach can pinpoint specific genetic changes that might lead to health issues. By discovering these changes, doctors can work to prevent or treat conditions before they become serious. Participants in this trial will have their genomes sequenced. If researchers identify an actionable genetic result, participants will be notified and offered the opportunity to have their research result clinically confirmed. ^{4 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for adults over 18 who are part of the Framingham Heart Study or Jackson Heart Study, have had their genomes sequenced by TOPMed, and consented to use their DNA for research. It's not open to those who haven't opted in for genomic research or haven't had genome sequencing through TOPMed.

Inclusion Criteria

I am over 18 years old.

I have agreed to use my DNA for research and to receive genetic information.

I am part of the Framingham or Jackson Heart Study and my genome has been sequenced in the TOPMed program.

Exclusion Criteria

I chose not to participate in genetic research.

Participants who did/do not consent to receiving a genomic result (for the gRoR portion of this study only)

I am part of the Framingham or Jackson Heart Study and my genome hasn't been sequenced by TOPMed.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Genomic Results Disclosure

Participants are notified of actionable genetic results and offered clinical confirmation

Up to 8 months

1 visit (in-person or virtual) for results disclosure

Follow-up

Participants are monitored for outcomes related to the disclosure of genomic results, including health care utilization and psychological impact

1 year

Surveys at 6 months and 1 year post-disclosure

Data Collection and Analysis

Collection and analysis of outcome and phenotypic data to explore genomic penetrance and other study objectives

Ongoing throughout the study

What Are the Treatments Tested in This Trial?

Interventions

• Genomic Sequencing

Trial Overview The PopSeq Project will give some participants their genomic results (gRoR) and study the medical, behavioral, and economic impacts. It involves interpreting previously sequenced genomes from two heart studies and assessing how genes manifest into physical traits in a group.

How Is the Trial Designed?

Group I: FHS & JHS participants with an actionable genomic finding Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

Brigham and Women's Hospital

Lead Sponsor

Trials

1,694

Recruited

14,790,000+

Framingham Heart Study

Collaborator

Trials

1

Recruited

110+

Jackson Heart Study

Collaborator

Trials

1

Recruited

110+

Broad Institute

Collaborator

Trials

21

Recruited

16,300+

University of Mississippi Medical Center

Collaborator

Trials

185

Recruited

200,000+

Broad Institute of MIT and Harvard

Collaborator

Trials

21

Recruited

16,300+

Partners HealthCare

Collaborator

Trials

15

Recruited

55,000+

Boston University

Collaborator

Trials

494

Recruited

9,998,000+

Published Research Related to This Trial

Pharmacogenomics can help predict adverse drug reactions (ADRs) by identifying genetic variations that affect how individuals respond to medications, addressing a significant issue in drug safety.

The review highlights successful examples of pharmacogenomics influencing clinical practice and discusses future areas where it could improve drug safety, while also acknowledging the challenges in implementing these tests in healthcare.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The emerging era of pharmacogenomics: current successes, future potential, and challenges. Lee, JW., Aminkeng, F., Bhavsar, AP., et al.[2021]

Genetic research is uncovering specific genes that influence how safely and effectively patients respond to medications, which can help prevent adverse drug reactions.

Primary care physicians are being targeted with advertisements for genetic tests that identify these variations, highlighting the need for a careful evaluation of these tests to ensure they are used optimally in patient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating pharmacogenetic tests: a case example. Freund, CL., Gregory, DF., Clayton, EW.[2019]

Serious adverse drug reactions are a leading cause of death in the USA and contribute significantly to healthcare costs, highlighting the need for better risk management in drug prescriptions.

Pharmacogenomic testing, which identifies genetic factors that affect drug response, is becoming increasingly important, with regulatory agencies pushing for mandatory testing for certain medications to prevent adverse reactions and improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacogenomics of adverse drug reactions: practical applications and perspectives. Becquemont, L.[2013]

Whole genome sequencing (WGS) is becoming the preferred method for identifying genetic variations due to its comprehensive nature and decreasing costs, moving away from traditional microarray-based genotyping.

There are two main approaches to assembling genomic sequences from short reads: de novo assembly, which builds sequences by overlapping reads, and reference-based assembly, which maps reads to a known genome, each with its own advantages and challenges.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Whole genome sequencing. Ng, PC., Kirkness, EF.[2022]

Human genomic sequencing can provide valuable insights for diagnosis, prognosis, and treatment across various medical fields, but its widespread use is limited by a lack of evidence showing improved patient outcomes in those without specific testing indications.

The paper reviews clinical outcome studies in genomic medicine, highlighting the challenges of generating robust evidence to support the integration of next-generation sequencing into standard patient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Building evidence and measuring clinical outcomes for genomic medicine. Peterson, JF., Roden, DM., Orlando, LA., et al.[2020]

The definition of an adverse drug event (ADE) should be tailored to the specific purpose of the evaluation, with stricter definitions needed for scientific studies and more flexible ones for clinical use.

Postmarketing safety data for drugs is limited at launch, but can be supplemented through systems like the FDA's Spontaneous Reporting System and targeted research projects, emphasizing the importance of robust epidemiological evidence for regulatory actions like drug recalls.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse drug events: identification and attribution. Rogers, AS.[2022]

Next-generation gene sequencing can sequence an individual's entire genome in under a week for $5000 to $10,000, making it a promising tool for diagnosing complex diseases that are hard to identify through traditional methods.

While there have been successful applications in diagnosing diseases and improving tumor management, significant challenges remain, including data interpretation, physician training, and the need for rigorous studies to validate its effectiveness in larger patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The promise and challenges of next-generation genome sequencing for clinical care. Johansen Taber, KA., Dickinson, BD., Wilson, M.[2022]

In a study of 52,942 patients over five years, 64.8% were prescribed at least one medication that could be influenced by genetic variants, highlighting the commonality of pharmacogenetic prescribing opportunities.

Implementing a preemptive genotyping program could potentially prevent 383 adverse events linked to specific medications, suggesting that this approach may enhance patient safety compared to traditional reactive methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing drug outcomes through pharmacogenetics: a case for preemptive genotyping. Schildcrout, JS., Denny, JC., Bowton, E., et al.[2022]

Whole exome sequencing can yield a substantial number of high-quality SNPs (single nucleotide polymorphisms) outside the targeted coding regions, with increases of 129% to 461% compared to SNPs within target regions across different sequencing platforms.

The study analyzed data from 22 subjects using Agilent SureSelect and 6 subjects using Illumina TrueSeq, revealing that these high-quality SNPs outside target regions are valuable and should be included in genetic epidemiology studies for a more comprehensive understanding of genetic variants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exome sequencing generates high quality data in non-target regions. Guo, Y., Long, J., He, J., et al.[2021]

Citations

1. bmcmedgenomics.biomedcentral.com bmcmedgenomics.biomedcentral.com/articles/10.1186/s12920-024-01795-w

Whole genome sequencing in clinical practice Whole genome sequencing (WGS) is becoming the preferred method for molecular genetic diagnosis of rare and unknown diseases and for ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10376292/

Next-Generation Sequencing Technology: Current Trends ... Next-generation sequencing (NGS) is a powerful tool used in genomics research. NGS can sequence millions of DNA fragments at once.

3. nature.com nature.com/articles/s41525-024-00404-0

Rapid genomic sequencing for genetic disease diagnosis ... Rapid genome sequencing (RGS), ultra-rapid genome sequencing (URGS), and rapid exome sequencing (RES) are diagnostic tests for genetic diseases ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1098360021046736

Are whole-exome and whole-genome sequencing ... We conducted a systematic literature review to summarize the current health economic evidence for whole-exome sequencing (WES) and whole-genome sequencing ...

5. genome.gov genome.gov/sites/default/files/media/files/2020-04/Guide_to_Interpreting_Genomic_Reports_Toolkit.pdf

Guide to Interpreting Genomic Reports: A Genomics Toolkit The use of genomic tests (gene panels, exome sequencing, genome sequencing) is increasing in the clinical and research setting. • An individual's genetic code ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4113721/

Genomic Sequencing: Assessing The Health Care System ... Our objective in this article is to provide a policy primer on sequencing and illustrate how it can affect health care system and policy issues.

7. medlineplus.gov medlineplus.gov/genetics/understanding/testing/sequencing/

What are whole exome sequencing and whole genome ... Two methods, whole exome sequencing and whole genome sequencing, are increasingly used in healthcare and research to identify genetic variations.

8. illumina.com illumina.com/techniques/sequencing/dna-sequencing/whole-genome-sequencing.html

Whole-Genome Sequencing (WGS) Whole-genome sequencing (WGS) is a comprehensive method for analyzing entire genomes, providing a comprehensive view of the entire genome.

9. mayocliniclabs.com mayocliniclabs.com/test-catalog/overview/616068

Whole Exome Sequencing for Hereditary Disorders, Varies WESDX is a test using next-generation sequencing to identify genetic disorders by detecting variants in 20,000 genes, aiding in diagnosis and management.