Population Genomic Screening is Here: We Need Evidence on Health Impact and Optimal Implementation

Posted on by Muin J. Khoury and W. David Dotson, Office of Genomics and Precision Public Health, Centers for Disease Control and Prevention, Atlanta, Georgia

a population with a double helix and genetic testingA recent study identified 12 population-based genomic screening programs in the United States and described their implementation logistics and potential health impact.

In the past decade, the promise of genomic screening in the general population has garnered increasing interest due to a combination of factors such as enhanced sequencing capabilities, lowered costs of testing, and expanded knowledge on clinical validity and utility of gene-disease associations. Beyond newborn screening, a case has been made that population genomic screening can lead to the diagnosis of selected hereditary disorders in 2-3% of the population.  This scenario has potential to save lives and reduce illness. However, evidence gaps in several areas (see Table 1) remain and need to be rigorously evaluated.

The study, conducted in 2020 and 2021, identified 12 population genomic screening programs across the United States (see Table 2). The study described features of each program using research implementation questions shown in Table 1. The authors present these questions as a general guide to help collect program information and describe trends across programs.

The pilot projects fell into 4 main groups: health systems with primary care enrollment, projects inviting a pre-defined number of patients to participate, statewide programs, and additional service in a genetics clinic. The number of genes chosen for screening ranged from 11 (with CDC tier 1 applications) to 59 (American College of Medical Genetics and Genomics secondary findings list v.2). These genes underwent exome or genome sequencing.

Regarding budgetary impact of genetic screening programs and out-of-pocket costs for patients, it was noted that:

  • Half of the programs are supported by institutional funding
  • Healthy Nevada, funded by Renown Health and Nevada Educational fund, offers free testing to all state residents.
  • The Alabama Genomic Health Initiative is funded by the state legislature.

Regarding patient engagement and recruitment, the study found that:

  • Primary care providers are key in seven programs, either at outpatient visits or by electronic messaging and social media.
  • Three programs focus on underserved, rural, and minority populations.

In addition, the study found that:

  • Almost all programs describe a formal consent process and personalized action plans and/or care pathways for positive results that include genetic counselors and primary care providers.
  • Six programs record results in electronic medical records to help ensure continuity of care and follow-up.
  • Six programs provide follow-up for possible changes in variant classification.

The main outcome reported by the 12 programs is the rate of medically actionable conditions. Some of the programs indicate they are assessing the efficacy and effectiveness of population genomic screening at the individual patient and health service outcome levels. Due to recency of some of these programs, short-term and long-term health outcomes (and other questions listed in Table 1) are largely unreported.

The present study provides an important initial step in assessing the landscape of population genomic screening in the US.  The authors acknowledge that additional programs have appeared since they started data collection and that additional information may be needed on the existing programs. One notable endeavor is the All of Us Research program, which is an NIH-led effort that is seeking to recruit up to a million people and follow them up longitudinally with return of genomic data. The genomic component of this massive study is just starting and will provide valuable information on the impact of population screening in a diverse population. Until recently, >90% of participants from large scale genomics projects have been of European descent. The All of Us Research program recently released whole genome sequence data on nearly 100,000 participants.  About 50% of the data is from individuals who identify with racial or ethnic groups that have historically been underrepresented in research.

In summary, several population-based programs are currently exploring the logistics and potential health impact of genomic screening in various health settings. The variability in health care settings, recruited populations, research protocols, and genes studies will yield important data to generate an evidence base for evaluating health outcomes and costs of population genomic screening. In addition, many barriers and facilitators to the implementation of population screening will have to be evaluated and addressed.  A collaborative approach across multiple programs and harmonized data collection will enhance the study of clinical validity and utility of genomic screening and implementation issues. Information sharing and joint analyses will accelerate the evaluation of genomic screening as a tool for improving population health.

Table 1: Twelve questions recommended to be addressed in pilot studies of population-based genomic screening (From Murray et al, 2019)

  1. How should screening be designed to offer inclusive benefits for the whole population (with specific attention to the poor, as well as underrepresented racial and ethnic groups)?
  2. What are the appropriate population characteristics for screening (eg, age, sex)?
  3. What is the optimal testing strategy/technology (eg, exome sequencing, multigene panel, single-nucleotide polymorphism array)?
  4. What are the ideal lead institutions for carrying out DNA-based screening (eg, health care provider organizations, departments of public health, for-profit companies)?
  5. How should DNA-based screening (primary screen) be paid for (eg, government funding, private insurance, self-pay)?
  6. How should clinical follow-up (secondary screen) be paid for (eg, government funding, private insurance, self-pay)?
  7. How often should data be reanalyzed (eg, compared with evolving databases like ClinVar [updated annually])?
  8. What strategy should be pursued for cascade testing (eg, should at-risk family members be automatically contacted by health system)?
  9. What are the short-term clinical outcomes (eg, correcting diagnostic misattribution, presymptomatic diagnosis of cancer or heart disease)?
  10. What are the long-term clinical outcomes (eg, nonpenetrance, overdiagnosis)?
  11. What are the best practices regarding negative screening result reporting (critically important to avoid false reassurance)?
  12. What are the clinical workforce needs related to delivering DNA-based results and clinical follow-up at population scale (ie, how many medical geneticists, genetic counselors, specialists, others)?


Table 2: Selected characteristics of 12 population genomic screening programs in the United States. (From Foss et al, 2022)

Program and Location Enrollment by Methodology Sample Size Goal
Geisinger MyCode, Danville, PA Providers Sequencing >250,000
University of Vermont The Genomic DNA Test, Burlington, VT Providers Sequencing 1000
University of California at San Francisco (UCSF) 3D Health, San Francisco, CA Patients/Providers Sequencing 1000
Sanford Health The Sanford Chip, Sioux Falls, SD Patients/Providers ACMG list + Pharmacogenomics Unknown
Northshore DNA10K, Chicago, IL Providers Sequencing 10,000
Oschner Health innovationOchsner Population Genomic Screening Program, New Orleans, LA Providers Sequencing 1000
Stanford University Humanwide, Palo Alto, CA Providers Sequencing 50
Healthy Nevada Project, Renown Health Patients/Providers Sequencing 250,000
Alabama Genomic Health Initiative, UAB Medicine Patients ACMG list 10,000
Brigham & Women’s Hospital Preventive Genomics Clinic, Boston, MA Patients Sequencing Unknown
St. Elizabeth Healthcare Precision Medicine and Genetics, Edgewood, KY Patients Sequencing Unknown
UCSF Preventive Genomics Clinic, San Francisco, CA Patients/Providers Sequencing Unknown


Posted on by Muin J. Khoury and W. David Dotson, Office of Genomics and Precision Public Health, Centers for Disease Control and Prevention, Atlanta, Georgia

2 comments on “Population Genomic Screening is Here: We Need Evidence on Health Impact and Optimal Implementation”

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    Note that the University of Vermont program’s screen evaluates 431 genes, far more than the max 59 genes implied.

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Page last reviewed: June 21, 2022
Page last updated: June 21, 2022