Skip directly to search Skip directly to A to Z list Skip directly to navigation Skip directly to page options Skip directly to site content

Hot Topics of the Day|PHGKB
Search PHGKB:


Hot Topics of the Day are picked by experts to capture the latest information and publications on public health genomics and precision health for various diseases and health topics. Sources include published scientific literature, reviews, blogs and popular press articles.

Sign up MyPHGKB to receive the daily hot topic email alert.

Search Archive:
Archived Hot Topics of the Day By Date
76 hot topic(s) found with the query "Population screening"

Genome-first evaluation with exome sequence and clinical data uncovers underdiagnosed genetic disorders in a large healthcare system
(Posted: Apr 21, 2024 0PM)

From the abstract: "Population-based genomic screening may help diagnose individuals with disease-risk variants. Here, we perform a genome-first evaluation for nine disorders in 29,039 participants with linked exome sequences and electronic health records (EHRs). We identify 614 individuals with 303 pathogenic/likely pathogenic or predicted loss-of-function (P/LP/LoF) variants, yielding 644 observations; 487 observations (76%) lack a corresponding clinical diagnosis in the EHR."

Evaluation of a two-step model of opportunistic genomic screening
M Martyn et al, EJHG, March 25, 2024 (Posted: Mar 25, 2024 8AM)

From the abstract: "Increasing use of diagnostic genomic sequencing is pushing health services to confront the issue of opportunistic genomic screening (OGS). To date, OGS has been offered concomitant with diagnostic testing. In contrast, we piloted a service offering OGS after return of diagnostic testing results. Evaluation was designed to provide insights for future models of service and included patient surveys at three time points, semi-structured interviews with genetic counsellors (GCs) and a focus group with medical scientists. Uptake was relatively low: 83 of 200 patients approached (42%) attended the OGS service, with 81 accepting OGS. "

Population Screening for Hereditary Hemochromatosis
Video Webinar, UNC Precision Public Health Network, (Posted: Mar 20, 2024 7AM)

From the website: " Current data suggest that 1 in 300 non-Hispanic White individuals in the United States carry a genetic variation in the HFE gene (C282Y homozygosity) that accounts for most cases of hereditary hemochromatosis (HH). This variation can lead to iron overload and life-threatening complications, such as severe liver disease. However, complications are preventable with early diagnosis and periodic phlebotomies to remove excess iron from the body. In this CDC webinar, speakers discussed how knowledge about HH has evolved since the discovery of the HFE gene in 1997, current opportunities for clinical and public health action to prevent disease, and future research priorities to advance case detection and reduce clinical complications from HH. "

Genetics Visit Uptake Among Individuals Receiving Clinically Actionable Genomic Screening Results.
Marci L B Schwartz et al. JAMA Netw Open 2024 3 (3) e242388 (Posted: Mar 18, 2024 3PM)

From the abstract: "What factors are associated with completion of a genetics visit in a population with positive genomic screening results? In this cohort study of a population genomic screening program including 1160 participants, several demographic and program-level factors were associated with the likelihood of completing a follow-up genetics visit. Desire to follow-up with primary care was the most frequently reported reason for declining to schedule a genetics visit. These findings suggest genomic screening programs may be more successful at supporting patients and clinicians in translating genetic results into clinical action by providing a framework for care coordination among primary care practitioners, genetics clinicians, and specialists."

Using implementation science to evaluate a population-wide genomic screening program: Findings from the first 20,000 In Our DNA SC participants.
Caitlin G Allen et al. Am J Hum Genet 2024 2 (Posted: Feb 03, 2024 9AM)

From the abstract: "Over 14 months, 20,478 participants enrolled, and 14,053 samples were collected. The majority selected at-home sample collection followed by clinical sample collection and collection at community events. Participants were predominately female, White (self-identified), non-Hispanic, and between the ages of 40-49. Participants enrolled through community events were the most racially diverse and the youngest. Half of those enrolled completed the program. We identified 137 individuals with pathogenic or likely pathogenic variants for CDC Tier 1 conditions. The majority (77.4%) agreed to genetic counseling, and of those that agreed, 80.2% completed counseling. "

Cost Effectiveness of Genomic Population Health Screening in Adults: A Review of Modeling Studies and Future Directions.
Robert S Wildin et al. J Appl Lab Med 2024 1 (1) 92-103 (Posted: Jan 09, 2024 9AM)

From the abstract: " Eight recent cost-effectiveness modeling studies for high penetrance monogenic dominant diseases that used input parameters from 3 different countries are reviewed. Results and their uses in refining implementations are analyzed and the roles for laboratory medicine in facilitating success are discussed. The reviewed studies generally found evidence for cost-effectiveness of genomic population health screening in at least a subset of their base case screening scenario. Sensitivity analyses identified opportunities for improving the likelihood of cost-effectiveness. On the whole, the modeling results suggest genomic population health screening is likely to be cost-effective for high penetrance disorders in younger adults."

Population screening requires robust evidence-genomics is no exception.
Clare Turnbull et al. Lancet 2023 12 (Posted: Dec 12, 2023 2PM)

From the article: "We argue that the complexities and uncertainties inherent to genomic prediction (of future disease risk) mean that rigorous, independent, and expert evaluation is just as essential for proposed population-level genomic screening approaches as for conventional disease screening (ie, for the detection of disease presence today), for which such evaluation is standard. "

Combined population genomic screening for three high-risk conditions in Australia: a modelling study
P Lacaze et al, e Clin Medicine, November 2023 (Posted: Nov 11, 2023 4PM)

From the abstract: "This modeling study assessed the impact of offering combined genomic screening for hereditary breast and ovarian cancer, Lynch syndrome and familial hypercholesterolaemia to all young adults in Australia, compared with the current practice of clinical criteria-based testing for each condition separately. Our findings suggest that offering combined genomic screening for high-risk conditions to young adults would be cost-effective in the Australian public healthcare system, at currently realistic testing costs. "

Ten Years of Incidental, Secondary, and Actionable Findings.
Sharon Plon et al. N Engl J Med 2023 11 (19) 1813-1814 (Posted: Nov 10, 2023 7AM)

From the paper: "The ACMG has highlighted the fact that the ACMG SF gene lists were not designed to be implemented for population screening outside of research. However, many of the genes that have an effect on life span are also considered to be “tier 1” by the Centers for Disease Control and Prevention; knowledge of their status could have a positive effect on population health. "

Actionable Genotypes and Their Association with Life Span in Iceland.
Brynjar O Jensson et al. N Engl J Med 2023 11 (19) 1741-1752 (Posted: Nov 09, 2023 2PM)

From the abstract: " In 2021, the American College of Medical Genetics and Genomics (ACMG) recommended reporting actionable genotypes in 73 genes associated with diseases for which preventive or therapeutic measures are available. Evaluations of the association of actionable genotypes in these genes with life span are currently lacking. In this study, we found that approximately 1 in 25 Icelanders carried an actionable genotype and that carrying such a genotype was associated with a reduced life span."

Risk perception and intended behavior change after uninformative genetic results for adult-onset hereditary conditions in unselected patients.
Nandana D Rao et al. Eur J Hum Genet 2023 9 (Posted: Sep 27, 2023 8AM)

From the abstract: "Overall, 2761 people received uninformative results and 1352 (49%) completed survey items. Respondents averaged 41 years old, 62% were female, and 56% were Non-Hispanic Asian. Results from the FACToR instrument showed mean (SD) scores of 0.92 (1.34), 7.63 (3.95), 1.65 (2.23), and 0.77 (1.50) for negative emotions, positive emotions, uncertainty, and privacy concerns, respectively, suggesting minimal psychosocial harms from genetic screening. Overall, 12.2% and 9.6% of survey respondents believed that their risk of cancer or heart disease, respectively, had changed after receiving their uninformative genetic screening results. Further, 8.5% of respondents planned to make healthcare changes and 9.1% other behavior changes. "

Assessing the Clinical Utility of Liquid Biopsies Across 5 Potential Indications From Therapy Selection to Population Screening: A Review.
David J Carr et al. JAMA Intern Med 2023 8 (Posted: Aug 29, 2023 11AM)

From the abstract: "Circulating tumor DNA tests are being promoted for multiple indications. Numerous studies are ongoing, but randomized clinical trials of their effect on patient-centered outcomes are rare. While these tests have the potential to improve care in selected indications, this must be proven, as they will add cost, complexity, and unintended adverse effects for patients."

Factors influencing genetic screening enrollment among a diverse, community-ascertained cohort: Factors influencing genetic screening enrollment
ND Rao et al, Public Health Genomics, August 21, 2023 (Posted: Aug 21, 2023 2PM)

Overall, learning about disease risk and identifying risk early for prevention purposes were important factors in decision-making to receive screening and regrets about screening and screening being against one’s moral code were not viewed as important. Although racial identity was challenging to assign in all cases, compared to other enrollees, African American and Asian enrollees considered test accuracy and knowing more about the test to be of greater importance. Three themes emerged related to nonparticipation: benefits do not outweigh risks, don’t want to know, and challenges with study logistics.

Is there clinical value in screening healthy children with genome sequencing compared with a gene panel for medically actionable pediatric conditions?
VK Malesu, News Medical, August 2, 2023 (Posted: Aug 04, 2023 9AM)

Is there a clinical value of screening ostensibly healthy newborns and children with genome sequencing in comparison with a gene panel for medically actionable pediatric conditions? In a recent study, genome sequencing uncovered potential pediatric-onset diagnoses in 8.2% of apparently healthy children, with 46.8% of findings associated with high-penetrance conditions. In contrast, only 2.1% of children screened with a panel of 268 genes for medically actionable pediatric conditions were found to be at risk for developing pediatric-onset disease, a significant difference.

Population screening shows risk of inherited cancer and familial hypercholesterolemia in Oregon
TD O'Brien et al, AJHG, July 27, 2023 (Posted: Jul 30, 2023 10AM)

The Healthy Oregon Project (HOP) is a statewide effort that aims to build a large research repository and influence the health of Oregonians through providing no-cost genetic screening to participants for a next-generation sequencing 32-gene panel comprising genes related to inherited cancers and familial hypercholesterolemia. Overall, we have identified 730 pathogenic/likely pathogenic variants in 710 participants in 24 of the 32 genes on the panel. The carrier rate for pathogenic/likely pathogenic variants in the inherited cancer genes on the panel for an unselected population was 5.0% and for familial hypercholesterolemia was 0.3%.

The Promise of Population-based Genomic Screening for Selected Hereditary Conditions: Contributions of Cost-Effectiveness Analysis
ND Rao et al, CDC Blog Post, July 14, 2023 Brand (Posted: Jul 14, 2023 1PM)

Initial cost-effectiveness research suggests that simultaneous population genomic screening for three CDC Tier 1 genomic applications (hereditary breast and ovarian cancer, Lynch syndrome, and familial hypercholesterolemia) can be cost effective and reduce morbidity and mortality if implemented in adults younger than 40 years old, costs of screening tests are low, and those found carrying a pathogenic variant have access to preventive care.

Age-Based Genomic Screening during Childhood: Ethical and Practical Considerations in Public Health Genomics Implementation
LV Milko et al, IJNS June 2023 (Posted: Jun 28, 2023 11AM)

Genomic sequencing offers an unprecedented opportunity to detect inherited variants that are implicated in rare Mendelian disorders, yet there are many challenges to overcome before this technology can routinely be applied in the healthy population. The age-based genomic screening (ABGS) approach is a novel alternative to genome-scale sequencing at birth that aims to provide highly actionable genetic information to parents over the course of their child’s routine health care. ABGS utilizes an established metric to identify conditions with high clinical actionability and incorporates information about the age of onset and age of intervention to determine the optimal time to screen for any given condition.

Medical and psychosocial outcomes of state-funded population genomic screening.
Ashley Cannon et al. Clin Genet 2023 6 (Posted: Jun 23, 2023 8AM)

Through the Alabama Genomic Health Initiative (AGHI), a state-funded genomic research program, individuals received screening for pathogenic or likely pathogenic variants in 59 actionable genes via genotyping. Of the 3874 eligible participants that received screening results, 858 (22%) responded to an outcomes survey. Participants with positive results reported a higher median number of planned actions (median = 5) due to AGHI results as compared to negative results (median = 3). Interviews were conducted with survey participants with positive screening results. As determined by certified genetic counselors, 50% of interviewees took appropriate medical action based on their result.

ACMG SF v3.2 list for reporting of secondary findings in clinical exome and genome sequencing: A policy statement of the American College of Medical Genetics and Genomics (ACMG)
DT Miller et al, Genetics in Medicine, June 22, 2023 (Posted: Jun 22, 2023 7AM)

The American College of Medical Genetics and Genomics (ACMG) previously published guidance for reporting secondary findings (SFs) in the context of clinical exome and genome sequencing. The ACMG Secondary Findings Working Group (SFWG) and Board of Directors (BODs) have agreed that the list of recommended genes should now be updated annually, but with an ongoing goal of maintaining this as a minimum list. Reporting of SFs should be considered neither a replacement for indication-based diagnostic clinical genetic testing nor a form of population screening.

Population-based Genomic Screening Programs: The Need for Optimal Implementation to Ensure Health Equity
N Rao et al, CDC Blog Post, June 20, 2023 Brand (Posted: Jun 20, 2023 1PM)

Differences in population genetic screening program design influence enrollment rates, particularly during the recruitment phase. In the absence of careful attention to how communities are engaged about genetic screening, population genetic screening may not reach all people, and existing health disparities could be widened. The effectiveness of population-wide screening to identify at-risk individuals will subsequently be diminished.

We Screen Newborns Don’t We? Progress in DNA-based Population Screening
Video presentations, CDC and Precision Public Health Network webinar, May 18, 2023 Brand (Posted: Jun 06, 2023 8AM)

As part of 2023 Public Health Genetics and Genomics week, presenters in this webinar review the concept of population genomic screening for rare diseases beyond the newborn period, share research progress made in the last decade, and discuss the path forward to prepare the medical and public health communities for population-based genomic screening.

Summary for Patients: Population Genomic Screening for Three Common Hereditary Conditions.
et al. Ann Intern Med 2023 5 (5) I19 (Posted: Jun 02, 2023 9AM)

Patients who have certain genetic test results are at higher risk for diseases that may be preventable. There is ongoing debate about whether physicians should screen for 3 hereditary conditions: Lynch syndrome (at greater risk for colon cancer), hereditary breast and ovarian cancer, and familial hypercholesterolemia (at greater risk for early heart disease and stroke). This modeling study found that screening for these 3 hereditary conditions is likely cost-effective in U.S. adults younger than 40 years if the testing cost is relatively inexpensive and people have access to preventive care.

Population Genomic Screening for Three Common Hereditary Conditions : A Cost-Effectiveness Analysis.
Gregory F Guzauskas et al. Ann Intern Med 2023 5 (Posted: May 09, 2023 5AM)

The cost-effectiveness of screening the U.S. population for Centers for Disease Control and Prevention (CDC) Tier 1 genomic conditions is unknown. We estimated the cost-effectiveness of simultaneous genomic screening for Lynch syndrome (LS), hereditary breast and ovarian cancer syndrome (HBOC), and familial hypercholesterolemia (FH). We found that population genomic screening with a restricted panel of high-evidence genes is likely to be cost-effective in U.S. adults younger than 40 years if the testing cost is relatively low and probands have access to preventive interventions.

Is it Time for Health Systems to Offer Preventive Genomic Screening?
CB Zawatsky et al, Genomes2People, April 2023 (Posted: Apr 16, 2023 6AM)

At this point, we can safely say that genomic screening can identify genetic risk factors that have direct medical screening and management implications. So what is holding health systems back from offering this type of testing clinically? Admittedly, there is still clinical utility data being collected to better understand all the implications and, yes, there is still the question of balancing sacred health care resources in a climate prone to health care provider burnout and overspending.

Diagnostic yield of genetic screening in a diverse, community-ascertained cohort
N Rao et al, MEDRXIV, December 2022 (Posted: Feb 13, 2023 2PM)

Overall, 40,857 people were invited and 2,899 (7.1%) enrolled. Enrollment varied across race and ethnicity groups, with the lowest enrollment among African American individuals (3.3%) and the highest among Multiracial or Other Race individuals (13.0%). Of 2,864 enrollees who received screening results, 106 actionable variants were identified in 103 individuals (3.6%). Of those who screened positive, 30.1% already knew about their results from prior genetic testing. The diagnostic yield was 74 new, actionable genetic findings (2.6%).

Population Screening for Rare Pathogenic Variants as the Low Hanging Fruit for Public Health Genomics Across the Lifespan
MJ Khoury, CDC Blog Post, February 13, 2023 Brand (Posted: Feb 13, 2023 11AM)

Using the rationale of newborn screening for rare disorders for which a specific combination of features pertain (serious outcome, effective prevention of diseases and disabilities, asymptomatic latent period, and an affordable assay), DNA-based population screening for rare pathogenic variants could be an early low hanging fruit for the emerging field of public health genomics.

Economic evaluation of population-based expanded reproductive carrier screening for genetic diseases in Australia
D Schofield et al, Genetics in Medicine, February 12, 2023 (Posted: Feb 13, 2023 7AM)

Expanded RCS was cost-saving compared with no population screening and cost-effective compared to the three-condition screening (ICER of $6,287 per QALY gained) at an uptake rate of 50% for RCS, 59% for IVF and preimplantation genetic testing, 90% for prenatal diagnosis testing and 50% for elective termination of affected pregnancies and a cost of A$595 per couple screened.

How Clinicians Conceptualize “Actionability” in Genomic Screening
K Owens et al, J Per Med, February 4, 2023 (Posted: Feb 05, 2023 11AM)

This research explores the social dynamics shaping the integration of “actionable” genomic data into primary care settings. Based on semi-structured interviews with 35 genetics experts and primary care providers, we find that clinicians vary in how they define and operationalize “actionable” information. There are two main sources of disagreement. First, clinicians differ on the levels and types of evidence required for a result to be actionable, such as when we can be confident that genomic data provides accurate information. Second, there are disagreements about the clinical actions that must be available so that patients can benefit from that information.

We Screen Newborns Don’t We? Progress in DNA-based Population Screening
CDC Public Health Genomics Webinar, May 18, 2023, Brand (Posted: Jan 28, 2023 11AM)

As part of 2023 Public Health Genetics and Genomics week, we review in this webinar the concept of population genomic screening for rare diseases beyond the newborn period, share research progress made in the last decade, and discuss the path forward to prepare the medical and public health communities for population-based genomic screening.

Prioritizing the detection of rare pathogenic variants in population screening.
Lacaze Paul et al. Nature reviews. Genetics 2023 1 (Posted: Jan 15, 2023 3PM)

Population genomic screening to detect carriers of rare monogenic variants for medically actionable conditions is supported by substantial evidence of clinical utility and cost effectiveness. Much less evidence supports screening by polygenic risk scores, which do not detect rare variants. Using only polygenic scores in population screening initiatives, while ignoring the detection of higher-risk rare monogenic variants, is ill-advised.

Medullary Thyroid Carcinoma and Population Screening-The Promise and Pitfalls of Genetic Testing.
Davies Louise et al. JAMA otolaryngology-- head & neck surgery 2023 1 (Posted: Jan 11, 2023 6AM)

Geisinger invited its members to consent to whole-exome sequencing and linked the findings with electronic health record information to identify future targets for medication development and other interventions to improve population health. Patients would be notified through a specifically established MyCode counseling program if they were found to have known, actionable genetic variants. The program has been popular; more than 270?000 Geisinger members have now signed up. The expected rate of actionable variants is approximately 3.5%. The popularity of the program suggests that as broader testing begins to penetrate US health care outside of specialized programs like the Geisinger one, we can expect to see many more patients in our offices who present after having learned they have one of these variants.

Real-World Results from Combined Screening for Monogenic Genomic Health Risks and Reproductive Risks in 300 Adults
RS Wildin et al, J Per Med, November 2022 (Posted: Nov 28, 2022 11AM)

This is the first report of genomic population screening in a primary care, non-research setting using existing large carrier and health risk gene sequencing panels combined into one 432-gene test that is offered to adults of any health status. This report summarizes basic demographic data and analyses patterns of pathogenic and likely pathogenic genetic findings for the first 300 individuals tested in this real-world scenario. Potential genetic health risks of various magnitudes for a broad range of disorders were identified in 16% to 34% of tested individuals.

Integrating genome-wide polygenic risk scores and non-genetic risk to predict colorectal cancer diagnosis using UK Biobank data: population based cohort study
SEW Briggs et al, BMJ, November 2022 (Posted: Nov 14, 2022 7AM)

Integrating polygenic risk scores with QCancer-10 modestly improves risk prediction over use of QCancer-10 alone. Given that QCancer-10 data can be obtained relatively easily from health records, use of polygenic risk score in risk stratified population screening for colorectal cancer currently has no clear justification. The added benefit, cost effectiveness, and acceptability of polygenic risk scores should be carefully evaluated in a real life screening setting before implementation in the general population.

EDITORIAL: DNA-based Population Screening for Precision Public Health
LV Milko et al, Frontiers in Genetics, October 14, 2022 (Posted: Oct 15, 2022 7AM)

Rapid advances, increasing availability, decreasing costs of sequencing technologies, computational pipelines for variant interpretation, and training of clinical personnel, are accelerating the integration of genomic sequencing into routine health care. Although genomic sequencing has demonstrated utility as an indication-based diagnostic tool for certain diseases, the full potential of DNA sequencing as a non-diagnostic tool for population-level screening is not yet realized. We hope our readers find the collection of papers herein useful in advancing the dialogue on DNA-based population screening towards a new era of precision public health.

Data-driven analysis of a validated risk score for ovarian cancer identifies clinically distinct patterns during follow-up and treatment
S Enroth et al, Comm Medicine, October 3, 2022 (Posted: Oct 04, 2022 8AM)

Ovarian cancer is the eighth most common cancer among women and due to late detection prognosis is poor with an overall 5-year survival of 30–50%. Novel biomarkers are needed to reduce diagnostic surgery and enable detection of early-stage cancer by population screening. We have previously developed a risk score based on an 11-biomarker plasma protein assay to distinguish benign tumors (cysts) from malignant ovarian cancer in women with adnexal ovarian mass.

Population Genetic Testing: Save Lives And Money, While Avoiding Financial Toxicity
E Matloff, Forbes, August 4, 2022 (Posted: Aug 07, 2022 8AM)

In theory, population genetic testing makes sense. Instead of waiting for a person to die of a heart attack at a young age, we can learn of some of those risks ahead of time and mitigate them. This approach works not only for the person having testing and their family members – who may also be at risk – but also for our medical system, employers, and overarching health care costs that we, as a society, want to minimize.

Population Genomic Screening is Here: We Need Evidence on Health Impact and Optimal Implementation
MJ Khoury et al, CDC Blog Post, June 21, 2022 Brand (Posted: Jun 21, 2022 3PM)

A 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

Barriers and facilitators for population genetic screening in healthy populations: a systematic review
EC Shen et al, Frontiers in Genetics, May 2022 (Posted: Jun 06, 2022 7AM)

Barriers and facilitators to population genetic screening were organized by the Social Ecological Model and further categorized by themes. We found that research in population genetic screening has focused on stakeholder attitudes with all included studies designed to elucidate individuals’ perceptions. Additionally, inadequate knowledge and perceived limited clinical utility presented a barrier for healthcare provider uptake. There were very few studies that conducted long-term follow-up and evaluation of population genetic screening.

Utilizing Public Health Frameworks and Partnerships to Ensure Equity in DNA-Based Population Screening
A Azriel et al, Frontiers in Genetics, May 2022 (Posted: Jun 06, 2022 7AM)

Potential actions to consider include: a) identification and elimination of systemic barriers that result in health inequities in DNA-based population screening and follow-up; b) creation of a national multidisciplinary advisory committee with representation from underserved communities; c) revisiting well-described public health screening principles and frameworks to guide new screening decisions and initiatives; d) inclusion of the updated Ten Essential Public Health Services with equity at the core in efforts at the local, state and national level.

DNA-based Population Screening for Precision Public Health
Milkow L, Khoury MJ (eds), Special Topic, Frontiers in Genetics, May 2022 (Posted: May 26, 2022 6AM)

DNA-based population screening to detect an individual's underlying predisposition to serious genetic conditions and improve health outcomes through risk assessment, early detection, and disease prevention, and timely treatment could accelerate the practice of precision public health. However, ascertainment of otherwise apparently healthy individuals with underlying genetic risk will necessitate a departure from the traditional model of familial or personal risk-based genetic testing in speciality settings to a population-based model of screening in primary care or community settings.

Positive predictive value highlights four novel candidates for actionable genetic screening from analysis of 220,000 clinicogenomic records
KMS Barrett et al, Genetics in Medicine, August 13, 2021 (Posted: Aug 13, 2021 8AM)

We identify 74 statistically significant gene–disease associations across 27 genes. Seven of these conditions have a positive predictive value (PPV) of at least 30% in both cohorts. Three are already used in population screening programs (BRCA1, BRCA2, LDLR), and we also identify four new candidates for population screening: GCK with diabetes mellitus, HBB with ß-thalassemia minor and intermedia, PKD1 with cystic kidney disease, and MIP with cataracts.

DNA-based Population Screening for Precision Public Health
Call for papers, Frontiers in Genetics, July 2021 (Posted: Jul 04, 2021 8AM)

Advancement and increasing availability of sequencing technologies, computational pipelines for variant interpretation, and training of clinical personnel, coupled with decreasing sequencing costs, have nudged genomic sequencing ever closer to the practice of routine health care. While genetic testing has demonstrated utility as an indication-based diagnostic tool for certain diseases, the full potential of genomic sequencing as a non-diagnostic tool for population-level screening is not yet realized.

RT-qPCR-based tests for SARS-CoV-2 detection in pooled saliva samples for massive population screening to monitor epidemics.
M Rosanski et al, MEDRXIV, May 9, 3031 (Posted: May 09, 2021 7AM)

Testing of 1475 individual clinical samples pooled in 374 pools of 4 revealed 0.8% false positive pools and no false negative pools. In weekly prophylactic testing of 113 people within 6 months, a two-tier testing approach enabled the detection of 18 infected individuals, including several asymptomatic individuals, with a fraction of the costs of individual RT-PCR testing.

From Genes to Public Health: Building the Evidence Base for DNA-based Population Screening
MJ Khoury et al, CDC Blog, April 9, 2021 Brand (Posted: Apr 10, 2021 7AM)

In the United States and other counties, the vision of DNA-based population screening has begun to be realized in multiple health systems, population-based biobanks and learning health systems research settings. Recently, the American College of Medical Genetics and Genomics published two guidance documents on DNA-based screening of healthy adults.

From genes to public health: are we ready for DNA-based population screening?
MJ Khoury et al, Genetics in Medicine, March 31, 2021 (Posted: Apr 01, 2021 0PM)

Two ACMG guidance documents reflect a new approach by marrying the importance of an evidence-based approach of the first document invoking principles of population screening with the importance of ensuring the integrity, quality, and outcomes of the testing process in the context of changing models of implementation.

Tier 1 Guidelines on Family-Based Screening for Hereditary Hemochromatosis
D Dotson et al, CDC Blog Post, March 12, 2021 Brand (Posted: Mar 14, 2021 0PM)

While our search identified no Tier 1 sources supporting population screening for HH, evidence-based guidelines do support Tier 1 designation for genetic counseling and testing of specific family members of people who are known to be p.C282Y homozygotes. The Tier 1 designation may also facilitate family-based awareness and diagnosis of HH and can influence clinical practice, as well as implementation research.

Assessment of an Online Tool to Simulate the Effect of Pooled Testing for SARS-CoV-2 Detection in Asymptomatic and Symptomatic Populations
CR Polage et al, JAMA Network Open, December 10, 2020 (Posted: Dec 10, 2020 11AM)

We created an online tool using actual SARS-CoV-2 virus copy number (VCN) data—the COVID19 Pool Tool—to help policy makers understand how pooled testing compares with single-sample testing in different populations. Pooled testing can extend SARS-CoV-2 test supplies and increase the number of patients tested and cases detected, making it useful for population screening and resource-constrained settings.

A state-based approach to genomics for rare disease and population screening.
East Kelly M et al. Genetics in medicine : official journal of the American College of Medical Genetics 2020 Nov (Posted: Nov 28, 2020 0PM)

The Alabama Genomic Health Initiative (AGHI) is a state-funded effort to provide genomic testing. AGHI engages two distinct cohorts across the state of Alabama. One cohort includes children and adults with undiagnosed rare disease; a second includes an unselected adult population. Here we describe findings from the first 176 rare disease and 5369 population cohort AGHI participants.

Are We Ready for Population Screening for Hereditary Hemochromatosis?
S Grosse et al, CDC Blog, September 28, 2020 Brand (Posted: Sep 28, 2020 11AM)

A CDC webinar calls attention to the large preventable burden of iron overload disease associated with HFE p.C282Y homozygosity. The natural history data presented here when paired with information on the effectiveness of phlebotomy for identified individuals can inform future discussions about population screening guidelines for HH.

Spread of SARS-CoV-2 in the Icelandic Population
DF. Gudbjartsson et al, NEJM, April 14, 2020 (Posted: Apr 15, 2020 7AM)

we used two strategies for SARS-CoV-2 testing— targeted testing of persons at high risk and population screening — which provided a gauge of success of measures implemented. We also sequenced the genomes of SARS-CoV-2 from samples obtained from some persons who had tested positive to establish virus origins and to determine how the virus has mutated as it has spread

Hereditary Hemochromatosis: Are We Ready for Population Screening?
CDC Seminar, January 15, 2019 Brand (Posted: Dec 13, 2019 8AM)

The iron overload seen in hemochromatosis can be treated, and even prevented, through phlebotomy. However, many with the condition do not know they have it and are not treated until after the iron overload has caused permanent damage. Is it time for population-based screening for the C282Y mutation?

DNA-Based Population Screening- Potential Suitability and Important Knowledge Gaps
MF Murray et al, JAMA, December 6, 2019 (Posted: Dec 06, 2019 0PM)

Optimized DNA-based population screening for selected genes has been proposed as an approach with the potential to offer short-term benefit for the estimated 3 to 4 million individuals in the United States with 1 of these risks and longer-term benefit to more people. However, many questions need to be answered before commencing with routine population screening.

Familial Hypercholesterolemia as a Prototype for Precision Public Health
MJ Khoury et al, CDC Blog, November 19, 2019 Brand (Posted: Nov 20, 2019 9AM)

In the absence of population screening guidelines specific to FH, and in the midst of all people with cholesterol-related health problems, how do we find and treat persons with FH? One answer to this question may be precision public health. Precision public health leverages emerging data by time, place, and persons, coupled with machine learning methods.

Factors Influencing Not Perceiving Family Health History Assessments as Important: Opportunities to Improve Dissemination of Evidence-Based Population Screening for Cancer
CG Allen et al, Public Health Genomics, May 2019 (Posted: May 05, 2019 11AM)

The use of ACMG secondary findings recommendations for general population screening: a policy statement of the American College of Medical Genetics and Genomics (ACMG)
ACMG Board of Directors, Genetics in Medicine, April 25, 2019 (Posted: Apr 25, 2019 9AM)

Factors Influencing Not Perceiving Family Health History Assessments as Important: Opportunities to Improve Dissemination of Evidence-Based Population Screening for Cancer.
Allen Caitlin G et al. Public health genomics 2019 Apr 1-10 (Posted: Apr 17, 2019 9AM)

Reconciling Opportunistic and Population Screening in Clinical Genomics.
Brothers Kyle B et al. Mayo Clinic proceedings 2019 Jan 94(1) 103-109 (Posted: Jan 09, 2019 10AM)

The case for population screening for BRCA, Lynch Syndrome, and FH
Color Genomics, YouTube, June 2018 (Posted: Aug 02, 2018 8AM)

Familial communication and cascade testing among relatives of BRCA population screening participants
S Lieberman et al, Genet in Medicine, Mar 29, 2018 (Posted: Mar 29, 2018 3PM)

Population Screening for Hereditary Colorectal Cancer.
Hampel Heather et al. Surgical oncology clinics of North America 2018 Apr 27(2) 319-325 (Posted: Mar 14, 2018 10AM)

Recommending inclusion of HFE C282Y homozygotes in the ACMG actionable gene list: cop-out or stealth move toward population screening?
AM Laberge, Genet Med, Oct 19, 2017 (Posted: Oct 20, 2017 9AM)

BRCA population screening for predicting breast cancer: for or against?
G Lippi et al, Ann Trans Med, July 2017 Brand (Posted: Aug 05, 2017 9AM)

BRCA population screening for predicting breast cancer: for or against?
Lippi Giuseppe et al. Annals of translational medicine 2017 Jul 5(13) 275 (Posted: Aug 02, 2017 8AM)

Utilization of genomic sequencing for population screening of immunodeficiencies in the newborn.
Pavey Ashleigh R et al. Genetics in medicine : official journal of the American College of Medical Genetics 2017 Jun (Posted: Jun 21, 2017 8AM)

Population screening for BRCA1/BRCA2 mutations: lessons from qualitative analysis of the screening experience.
Lieberman Sari et al. Genetics in medicine : official journal of the American College of Medical Genetics 2017 Jun (6) 628-634 (Posted: Jun 10, 2017 9AM)

Ashkenazi Jewish population screening for Tay-Sachs disease: the international and Australian experience.
Lew Raelia M et al. Journal of paediatrics and child health 2015 Mar 51(3) 271-9 (Posted: Dec 29, 2015 4PM)

Genetic testing all women for breast cancer might not be worth the cost
Science Daily, September 3, 2015 (Posted: Sep 10, 2015 1PM)

Cost-effectiveness of Universal BRCA1/2 Screening - Evidence-Based Decision Making
EF Long et al. JAMA Oncology, September 3, 2015 (Posted: Sep 03, 2015 3PM)

Can we use genetic stratification in population screening for cancer?
Brand (Posted: Feb 25, 2015 0PM)

Population testing for cancer predisposing BRCA1/BRCA2 mutations in the Ashkenazi-Jewish community: a randomized controlled trial.
Manchanda Ranjit et al. J. Natl. Cancer Inst. 2015 Jan (1) 379 (Posted: Feb 16, 2015 8AM)

Cost-effectiveness of population screening for BRCA mutations in Ashkenazi jewish women compared with family history-based testing.
Manchanda Ranjit et al. J. Natl. Cancer Inst. 2015 Jan (1) 380 (Posted: Feb 16, 2015 8AM)

Population-based screening for BRCA1 and BRCA2: 2014 Lasker Award.
King Mary-Claire et al. JAMA 2014 Sep 17. (11) 1091-2 (Posted: Feb 16, 2015 8AM)

Lasker Award winner Mary-Claire King.
King Mary-Claire et al. Nat. Med. 2014 Oct (10) 1124-5 (Posted: Feb 16, 2015 8AM)

Population-based screening for breast and ovarian cancer risk due to BRCA1 and BRCA2.
Gabai-Kapara Efrat et al. Proc. Natl. Acad. Sci. U.S.A. 2014 Sep 30. (39) 14205-10 (Posted: Feb 16, 2015 8AM)

Precision medicine meets public health: population screening for BRCA1 and BRCA2.
Levy-Lahad Ephrat et al. J. Natl. Cancer Inst. 2015 Jan (1) 420 (Posted: Feb 16, 2015 8AM)

A Never-Ending Genetic Quest. Mary-Claire King?s Pioneering Gene Work, From Breast Cancer to Human Rights
New York times, February 9, 2015 (Posted: Feb 16, 2015 8AM)

Disclaimer: Articles listed in Hot Topics of the Day are selected by Public Health Genomics Branch to provide current awareness of the scientific literature and news. Inclusion in the update does not necessarily represent the views of the Centers for Disease Control and Prevention nor does it imply endorsement of the article's methods or findings. CDC and DHHS assume no responsibility for the factual accuracy of the items presented. The selection, omission, or content of items does not imply any endorsement or other position taken by CDC or DHHS. Opinion, findings and conclusions expressed by the original authors of items included in the Clips, or persons quoted therein, are strictly their own and are in no way meant to represent the opinion or views of CDC or DHHS. References to publications, news sources, and non-CDC Websites are provided solely for informational purposes and do not imply endorsement by CDC or DHHS.