Population genomic screening is a way to examine the DNA of a large number of individuals to find genetic changes that may increase the risk for certain health conditions where early detection or prevention is possible. This method aims to identify people who are unaware they are at risk for serious diseases but could benefit from early detection or prevention.

Genomic screening for large groups is becoming more common in health care as the cost of DNA testing goes down and technology improves. While still new in many places, population genomic screening has already been used in large pilot programs in health care systems in the United States, the United Kingdom, Australia, and many other countries.

As population genomic screening expands, it offers promise for finding diseases earlier and helping people take steps to protect their health and the health of their families. By uncovering hidden risks, this approach can help people take steps to protect their health and improve health outcomes for individuals and communities.

Population genomic screening is a process that tests the DNA of individuals for diseases that have not yet occurred or been diagnosed. The main goal is to find genetic changes that increase the risk of developing health problems that can be prevented or treated more effectively if found early.

Unlike testing that targets people with a known family history, population genomic screening is offered to everyone in a group—such as all adults in a certain area or below a certain age—regardless of their medical background. The screening focuses on specific genetic changes that are linked to diseases where early action can make a difference.

This kind of screening does not diagnose diseases. Instead, it identifies people who have a higher chance of developing certain conditions in the future. If a person is found to have a genetic change tied to a higher risk, they may be able to take steps to reduce that risk or detect disease earlier if it develops.

Population genomic screening is used as a public health tool. It aims to find health risks before symptoms appear and uses advances in DNA technology and genetic science to help people learn about their health in a proactive way.

There are different types of genetic testing, each with its own purpose:

• Diagnostic genetic testing: Used for people who already have symptoms. It helps identify the genetic cause of those symptoms.
• Carrier screening: Checks for genetic changes that can be passed on to children, even if the person tested does not have symptoms. This is often used before or during pregnancy.
• Newborn screening: A public health program that tests newborns for certain rare but serious conditions that can be treated early. It uses a small blood sample collected soon after birth.
• Direct-to-consumer genetic testing: These are tests that people can order themselves, often to learn about ancestry or certain health traits. The results usually are not reviewed by a health care provider and typically require clinical confirmation for medical use.
• Population genomic screening: Offered to large groups of people, this screening looks for genetic risks for serious but preventable diseases. It is typically overseen by health care professionals and focuses on genetic changes where there are proven steps that can be taken to lower risk or monitor for early signs of disease.

Population genomic screening is different because it is designed to find people at risk before disease starts, rather than only testing those with symptoms or a strong family history.

Population genomic screening is offered to a wide group of people, not just those already known to be at high risk. The purpose is to identify hidden genetic risks in the general population.

The process often begins by inviting people in a community, health system, or region to participate. Participants give a sample, usually blood, which is sent to a laboratory for analysis. The lab examines the sample for changes in certain genes known to raise the risk of diseases that can be prevented or treated if found early.

Screening many people helps find those who would be missed by standard approaches, such as symptom-based testing or family history-based testing. Many people with important genetic risks do not have symptoms or a known family history, so population screening gives people who would likely not otherwise participate in genetic testing a chance to learn about their risks.

When a genetic change is found, the participant is contacted and given information about what it means and possible next steps. This may include a discussion with a genetic counselor or a doctor to talk about care or prevention. Since genetic material is shared between family members, the results of genetic tests can also have important implications for the participant’s children, siblings, and other blood relatives.

By screening the population, individuals can take action earlier to manage or even prevent deadly diseases.

Population genomic screening is designed to find risks for conditions where early action can make a difference. Some of the most common conditions include:

• Hereditary breast and ovarian cancer: Caused by changes in genes such as BRCA1 and BRCA2, these cancers can occur at younger ages. Knowing about a risk can help people get regular screening or consider preventive options.
• Familial hypercholesterolemia: A genetic change that leads to very high cholesterol and early heart disease. Early treatment with changes in diet, lifestyle, and medication can help prevent heart attacks and strokes.
• Lynch syndrome: This genetic condition raises the risk for colorectal and other cancers. Early identification allows for more frequent screening and, in some cases, preventive surgery.
• Hereditary transthyretin amyloidosis (hATTR): A rare disease, more common in some populations, that causes buildup of abnormal protein in the body and can affect the heart and nerves. Early detection can lead to treatments that may slow disease progression and improve outcomes.

These conditions are considered “medically actionable,” meaning there are established ways to lower the risk or catch the disease early. As research continues, population genomic screening may be used for more conditions in the future.

Population genomic screening involves several steps to make sure the process is accurate and respects each person’s rights.

First, people are given information about the screening and asked if they want to participate. This is called consent. People should understand what the test will look for, what the results might mean, and how their genetic data will be protected.

Next, participants provide a sample, usually saliva or a small blood sample. The sample is sent to a laboratory that specializes in genetic testing, where it is checked for changes in genes related to certain diseases.

If the initial test finds a possible risk, additional testing may be done to confirm the result. This confirmatory testing helps ensure that only accurate results are reported to participants.

When results are ready, participants are usually contacted by a health care professional, such as a genetic counselor or doctor. The results are explained in detail, and the participant is advised about next steps. This may include further testing, changes in health care, or sharing information with family members if relevant.

The process is designed to be clear, accurate, and supportive, with strong communication and counseling, especially for results that may affect both the participant and their relatives.

Population genomic screening is meant for people who do not have clearly defined symptoms of disease and may not have a family history of the conditions being screened. It can be offered to adults, and in some cases, to children, depending on the specific condition.

Some programs focus on adults, while others may include children or teenagers, especially if early treatment is important for the condition.

Anyone thinking about population genomic screening should consider what the results could mean for them and their families, and discuss questions or concerns with a health care professional before participating.

Population genomic screening can produce several types of results. Understanding these results helps people make informed decisions about their health.

• Positive result: The person has a genetic change known to increase the risk for a specific condition. This does not mean they will definitely develop the condition, but their risk is higher than average. Additional steps are needed to confirm the result and decide on a plan.
• Negative result: No genetic changes linked to the conditions being screened were found. This lowers the chance of developing those diseases, but does not guarantee the person will never get them. Other factors, such as lifestyle and non-genetic causes, may still play a role.
• Uncertain result (variant of uncertain significance): Sometimes, a genetic change is found, but it is not clear whether it increases disease risk. These are called variants of uncertain significance, or VUS. Usually, these results do not change care but may be reviewed again in the future as science advances.

People should review their results with a health care professional, who can explain what the findings mean and what actions, if any, are recommended.

If a person receives a positive result from population genomic screening, several important steps should be taken:

• Confirm the result: Sometimes, a second test in a certified laboratory is needed to make sure the result is correct.
• Meet with a clinician or genetic counselor: A health care professional can explain the meaning of the result, discuss the level of risk, and help decide on next steps. This may include reviewing personal and family medical history.
• Consider risk management options: Depending on the condition, options may include regular health checks, lifestyle changes, medication, or preventive procedures. The health care team will guide each person based on their individual risk.
• Understand penetrance: Having a genetic change does not guarantee that a person will develop the disease. Penetrance is the chance that someone with the change will actually have the condition. The health care team can explain the specific risk.
• Inform family members: Some genetic changes can be passed on to family members. The health care provider may suggest that close relatives consider testing (called cascade testing) to find out if they are at risk. This can help family members take steps to protect their health.
• Seek support: Learning about a higher risk for disease can be emotional. Support from health care professionals, counselors, and support groups can help people cope and make informed decisions.

Following these steps can help people use their results to protect their own health and, in some cases, help their family members as well.

Risks and limitations of population genomic screening include:

• False positives: A test may suggest a risk that is not real, leading to unnecessary worry or extra testing.
• False negatives: A person may have a negative result but still develop the condition due to other factors or gene changes not covered by the test.
• Uncertain findings: Some results may be unclear (variants of uncertain significance), which can cause confusion or anxiety while waiting for more information.
• Variable penetrance (how likely a person with a genetic change is to develop the condition): Not everyone with a genetic change will develop the disease. The likelihood can vary by gene and person, and can be influenced by other non-genetic factors. A positive result means the person has a higher risk of developing the disease, but does not mean they will definitely develop it.
• Emotional impact: Finding out about an increased risk for disease can cause stress, anxiety, or worry for both the individual and their family.
• Need for follow-up care: Positive or uncertain results often require more tests, regular check-ups, or preventive steps. This can be time-consuming and may require access to specialized care.
• Privacy and data concerns: Genetic information is sensitive. Programs must protect privacy and ensure data is stored and shared securely.
• Equity and access: Not everyone has equal access to screening or follow-up care. Some groups may face more barriers due to cost, location, or other factors.

It is important for people to understand these risks and limitations before deciding to participate in population genomic screening. Speaking with a health care professional can help answer questions and provide support in making informed choices.

This article was reviewed by Caroline Hendry, PhD, Scientific Director and Director of the Office for Strategy and Research Development at the Yale School of Medicine Department of Genetics.