Polygenic Risk Score Testing for High Genetic Risk of Diseases
(GenoVA Trial)
Recruiting in Palo Alto (17 mi)
Overseen byJason L. Vassy, MD, MPH, SM
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: Harvard Medical School
Disqualifiers: Coronary artery disease, Atrial fibrillation, Type 2 diabetes, Colorectal cancer, Breast cancer, others
No Placebo Group
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?This trial will determine the clinical effectiveness of polygenic risk score testing among patients at high genetic risk for at least one of six diseases (coronary artery disease, atrial fibrillation, type 2 diabetes mellitus, colorectal cancer, breast cancer, or prostate cancer), measured by time-to-diagnosis of prevalent or incident disease over 24 months.
Will I have to stop taking my current medications?
The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators for more details.
What data supports the effectiveness of the treatment Polygenic Risk Score Testing for High Genetic Risk of Diseases?
Research shows that polygenic risk scores (PRS) can help predict the risk of complex diseases like heart disease, diabetes, and cancer by combining genetic information. While PRSs are increasingly used in clinical settings, their effectiveness is still being evaluated, and they are not yet widely adopted in routine clinical practice.
12345Is polygenic risk score testing safe for humans?
There is no specific safety data available for polygenic risk score testing, as it is primarily a tool for predicting genetic risk rather than a treatment. It is used to guide healthcare decisions and does not involve any direct intervention in the body.
23567How is the polygenic risk score treatment different from other treatments for genetic risk of diseases?
Polygenic risk score (PRS) treatment is unique because it uses a person's genetic information to estimate their risk for complex diseases by analyzing thousands of genetic variants, unlike traditional treatments that may not consider genetic factors. This approach can help tailor healthcare decisions based on an individual's genetic susceptibility, offering a more personalized strategy compared to standard treatments.
12389Eligibility Criteria
This trial is for individuals aged 50-70 who have a high genetic risk but no current diagnosis of coronary artery disease, atrial fibrillation, type 2 diabetes, colorectal cancer, breast cancer, or prostate cancer. Pregnant individuals, those incarcerated or institutionalized, and anyone with a known diagnosis of these diseases cannot participate.Inclusion Criteria
I do not have a history of heart disease, irregular heartbeat, diabetes, or cancer.
I have no history of heart disease, diabetes, or certain cancers.
I am between 50 and 70 years old.
Exclusion Criteria
I have been diagnosed with one of the six specified diseases.
Pregnancy
You are currently in jail or a mental health facility.
+1 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Baseline Assessment
Participants and providers receive PRS results and educational resources
1 week
1 visit (in-person)
Observation
Participants are monitored for changes in clinical management and time-to-diagnosis of diseases
24 months
Regular follow-ups as per study protocol
Follow-up
Participants are monitored for safety and effectiveness after the main observation period
4 weeks
Participant Groups
The study is testing the effectiveness of polygenic risk score (PRS) testing in predicting the development of six different diseases over two years. It aims to see if PRS can help identify these conditions earlier among people at high genetic risk.
4Treatment groups
Experimental Treatment
Active Control
Group I: Polygenic risk score (PRS) - high risk stratumExperimental Treatment1 Intervention
Patient-participants in the PRS-high arm and their providers will receive their high-PRS results at baseline, along with educational resources about the results.
Group II: Polygenic risk score (PRS) - average risk stratumExperimental Treatment1 Intervention
Patient-participants in the PRS-average arm and their providers will receive their average-PRS results at baseline, along with educational resources about the results.
Group III: Usual care (UC) - high risk stratumActive Control1 Intervention
Patient-participants in the UC-high arm and their providers will receive their high-PRS results after a 24-month observation period, along with educational resources about the results.
Group IV: Usual care (UC) - average risk stratumActive Control1 Intervention
Patient-participants in the UC-average arm and their providers will receive their average-PRS results after a 24-month observation period, along with educational resources about the results..
Polygenic risk score (PRS) is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Polygenic Risk Score for:
- Coronary artery disease
- Atrial fibrillation
- Type 2 diabetes mellitus
- Colorectal cancer
- Breast cancer
- Prostate cancer
🇪🇺 Approved in European Union as Polygenic Risk Score for:
- Cardiovascular diseases
- Diabetes
- Cancer risk assessment
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
VA Boston Healthcare SystemBoston, MA
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Who Is Running the Clinical Trial?
Harvard Medical SchoolLead Sponsor
Harvard Medical School (HMS and HSDM)Lead Sponsor
Boston VA Research Institute, Inc.Lead Sponsor
VA Boston Healthcare SystemCollaborator
References
The emerging field of polygenic risk scores and perspective for use in clinical care. [2021]Genetic testing is used widely for diagnostic, carrier and predictive testing in monogenic diseases. Until recently, there were no genetic testing options available for multifactorial complex diseases like heart disease, diabetes and cancer. Genome-wide association studies (GWAS) have been invaluable in identifying single-nucleotide polymorphisms (SNPs) associated with increased or decreased risk for hundreds of complex disorders. For a given disease, SNPs can be combined to generate a cumulative estimation of risk known as a polygenic risk score (PRS). After years of research, PRSs are increasingly used in clinical settings. In this article, we will review the literature on how both genome-wide and restricted PRSs are developed and the relative merit of each. The validation and evaluation of PRSs will also be discussed, including the recognition that PRS validity is intrinsically linked to the methodological and analytical approach of the foundation GWAS together with the ethnic characteristics of that cohort. Specifically, population differences may affect imputation accuracy, risk magnitude and direction. Even as PRSs are being introduced into clinical practice, there is a push to combine them with clinical and demographic risk factors to develop a holistic disease risk. The existing evidence regarding the clinical utility of PRSs is considered across four different domains: informing population screening programs, guiding therapeutic interventions, refining risk for families at high risk, and facilitating diagnosis and predicting prognostic outcomes. The evidence for clinical utility in relation to five well-studied disorders is summarized. The potential ethical, legal and social implications are also highlighted.
A polygenic risk score for Alzheimer's disease constructed using APOE-region variants has stronger association than APOE alleles with mild cognitive impairment in Hispanic/Latino adults in the U.S. [2023]Polygenic Risk Scores (PRSs) are summaries of genetic risk alleles for an outcome.
Genotype imputation and variability in polygenic risk score estimation. [2022]Polygenic risk scores (PRSs) are a summarization of an individual's genetic risk for a disease or trait. These scores are being generated in research and commercial settings to study how they may be used to guide healthcare decisions. PRSs should be updated as genetic knowledgebases improve; however, no guidelines exist for their generation or updating.
Polygenic risk scores: from research tools to clinical instruments. [2021]Genome-wide association studies have shown unequivocally that common complex disorders have a polygenic genetic architecture and have enabled researchers to identify genetic variants associated with diseases. These variants can be combined into a polygenic risk score that captures part of an individual's susceptibility to diseases. Polygenic risk scores have been widely applied in research studies, confirming the association between the scores and disease status, but their clinical utility has yet to be established. Polygenic risk scores may be used to estimate an individual's lifetime genetic risk of disease, but the current discriminative ability is low in the general population. Clinical implementation of polygenic risk score (PRS) may be useful in cohorts where there is a higher prior probability of disease, for example, in early stages of diseases to assist in diagnosis or to inform treatment choices. Important considerations are the weaker evidence base in application to non-European ancestry and the challenges in translating an individual's PRS from a percentile of a normal distribution to a lifetime disease risk. In this review, we consider how PRS may be informative at different points in the disease trajectory giving examples of progress in the field and discussing obstacles that need to be addressed before clinical implementation.
Polygenic risk scores: An overview from bench to bedside for personalised medicine. [2023]Since the first polygenic risk score (PRS) in 2007, research in this area has progressed significantly. The increasing number of SNPs that have been identified by large scale GWAS analyses has fuelled the development of a myriad of PRSs for a wide variety of diseases and, more recently, to PRSs that potentially identify differential response to specific drugs. PRSs constitute a composite genomic biomarker and potential applications for PRSs in clinical practice encompass risk prediction and disease screening, early diagnosis, prognostication, and drug stratification to improve efficacy or reduce adverse drug reactions. Nevertheless, to our knowledge, no PRSs have yet been adopted into routine clinical practice. Beyond the technical considerations of PRS development, the major challenges that face PRSs include demonstrating clinical utility and circumnavigating the implementation of novel genomic technologies at scale into stretched healthcare systems. In this review, we discuss progress in developing disease susceptibility PRSs across multiple medical specialties, development of pharmacogenomic PRSs, and future directions for the field.
Generalisation of genomic findings and applications of polygenic risk scores. [2023]Polygenic Risk Scores (PRS) (also known as polygenic scores, genetic risk scores or polygenic indexes) capture genetic contributions of a multitude of markers that characterise complex traits. Although their likely application to precision medicine remains to be established, promising advances have included their ability to stratify high risk individuals and targeted screening interventions. Current PRS have been mostly optimised for individuals of Northern European ancestries. If PRS are to become widespread as a tool for healthcare applications, more diverse populations and greater capacity for derived interventions need to be accomplished. In this editorial we aim to attract submissions from the research community that highlight current challenges in development of PRS applications at scale. We also welcome manuscripts that delve into the ethical, social and legal implications that the implementation of PRS may generate.
Statistical genetics and polygenic risk score for precision medicine. [2021]The prediction of disease risks is an essential part of personalized medicine, which includes early disease detection, prevention, and intervention. The polygenic risk score (PRS) has become the standard for quantifying genetic liability in predicting disease risks. PRS utilizes single-nucleotide polymorphisms (SNPs) with genetic risks elucidated by genome-wide association studies (GWASs) and is calculated as weighted sum scores of these SNPs with genetic risks using their effect sizes from GWASs as their weights. The utilities of PRS have been explored in many common diseases, such as cancer, coronary artery disease, obesity, and diabetes, and in various non-disease traits, such as clinical biomarkers. These applications demonstrated that PRS could identify a high-risk subgroup of these diseases as a predictive biomarker and provide information on modifiable risk factors driving health outcomes. On the other hand, there are several limitations to implementing PRSs in clinical practice, such as biased sensitivity for the ethnic background of PRS calculation and geographical differences even in the same population groups. Also, it remains unclear which method is the most suitable for the prediction with high accuracy among numerous PRS methods developed so far. Although further improvements of its comprehensiveness and generalizability will be needed for its clinical implementation in the future, PRS will be a powerful tool for therapeutic interventions and lifestyle recommendations in a wide range of diseases. Thus, it may ultimately improve the health of an entire population in the future.
Could Polygenic Risk Scores Be Useful in Psychiatry?: A Review. [2022]Polygenic risk scores (PRS) are predictors of the genetic susceptibility to diseases, calculated for individuals as weighted counts of thousands of risk variants in which the risk variants and their weights have been identified in genome-wide association studies. Polygenic risk scores show promise in aiding clinical decision-making in many areas of medical practice. This review evaluates the potential use of PRS in psychiatry.
From Basic Science to Clinical Application of Polygenic Risk Scores: A Primer. [2022]Polygenic risk scores (PRS) are predictors of the genetic susceptibilities of individuals to diseases. All individuals have DNA risk variants for all common diseases, but genetic susceptibility differences between people reflect the cumulative burden of these. Polygenic risk scores for an individual are calculated as weighted counts of thousands of risk variants that they carry, where the risk variants and their weights have been identified in genome-wide association studies. Here, we review the underlying basic science of PRS, providing a foundation for understanding the potential clinical utility and limitations of PRS.