The ability to extract your DNA from a blood sample and use it to analyze your risk for a disease is one of the most promising developments in preventive medicine. You might learn, for example, that you are at a higher risk for developing breast cancer or a type of heart disease. Armed with that knowledge, you can then talk to a specialist about monitoring your health and take steps to prevent it.
Of course, geneticists are far from being able to perform genetic screening for every one of the many thousands of diseases out there, but in a field that still sounds like science fiction, people are often surprised at what is already possible.
At Yale, a project called “Generations” is performing a 10-gene analysis to provide people with information about their risk for 10 diseases, all of them heart- or cancer-related. Anyone is eligible and the analysis is free of charge.
“This is a chance to learn about risks that you wouldn't otherwise know you had,” says Michael Murray, MD, a Yale Medicine geneticist and clinical director of the Yale Center for Genomic Health. He became the leader of the Generations Project at Yale after heading up a similar project at Geisinger Health in Pennsylvania, where he helped lead the effort to create a biobank containing genetic data from more than 50,000 patients. “Waiting until someone gets cancer or heart disease is not a very good way to approach the problem,” he says. “Doing something about it sooner is what we all want to get to.”
Dr. Murray’s goal for Yale is to enroll at least 100,000 volunteers of any age or health status in the Generations Project, working in collaboration with Yale Medicine, Yale School of Medicine, and Yale New Haven Health. In addition to providing participants with the results of their genetic screenings, he plans to build a research dataset here that he expects will be valuable for both treatment and research. The project has about 4,000 volunteers already.
Yong-Hu Jiang, MD, PhD, chief of medical genetics at Yale, expects the number of enrollees to grow over time—and the list of genes the project analyzes to expand as scientists learn more about genetic predispositions and the best treatments for the conditions they are associated with. “Hospitals are following this kind of work very closely, and you will eventually see more and more integration of genomic medicine into all types of medical practices,” Dr. Jiang says.
The Yale Generations Project screens 10 genes
The 10 genes Generations is screening may seem like a small number if you consider that the human genome contains 20,000 genes. But this is just the start; the project will be periodically expanding its list over time as knowledge grows. And the project purposely chose these 10 genes because they are associated with risks for conditions patients can take steps to prevent, Dr. Murray says.
For example, people who learn they have a BRCA mutation, which predisposes them to breast and other cancers, can consult with the appropriate specialists, have the proper tests, and either take steps to prevent cancer or diagnose it early when it's most easily treatable, Dr. Murray says. “That’s the basic strategy.”
The Centers for Disease Control and Prevention (CDC), the American College of Medical Genetics, and other organizations have created similar lists for general genetic screening based partly on the fact that experts know enough about them to recommend steps to prevent them, Dr. Murray says.
Screening is simple for the participant
For participants, the screening process is easy. They complete a consent process. They are then given instructions for providing a DNA sample (either blood or saliva). And they agree to allow the data to be used for both their care and for research to discover new ways to help promote health.
The usual timeline for results is two months, and the Generations team is available to interpret and explain them to the participant. The latter step is important, says Monica Giovanni, MS, a certified genetics counselor and genomic strategy consultant for Generations. “If you test positive for breast cancer risk based on a BRCA genetic mutation, that does not necessarily mean you will develop breast cancer in your life,” she says. “It just increases your risk above the general population. Based on that, we can offer screening and early interventions to keep you healthy longer.” People who get a positive result may make different decisions on how to proceed based on such factors as how old they are, their personal or family health history, and their life goals, Giovanni says.
Knowledge is power—that’s what we hope people will get from this and value from it. Michael Murray, MD, clinical director of the Yale Center for Genomic Health
Anyone who is nervous about getting a positive result should know that only 1 to 2% of the few thousand people Generations has screened so far have learned they have one of the 10 genetic variations, Dr. Murray says. “So, 98 to 99% of people get a letter in the mail saying, ‘You were screened for these 10 genes, and we didn't find anything to worry about,’” he says.
The small number of people who have a positive result are invited to consult with the Generations team. “We give people information—explain what it means and tell them what the next steps are—and help them get to the specialists they need,” Dr. Murray says. One clear recommendation for everyone is to plan for routine, long-term follow-up with a clinical expert. If a participant learns they have one of the two BRCA gene mutations, for example, they are usually referred to a specialist who can both carry out an in-depth initial evaluation and then help them manage their risk over the long-term.
“If you know your risk, you can be monitored or treated to prevent a bad outcome,” says Dr. Jiang. “If it’s a heart condition, for example, a cardiologist may be able to offer an immediate, potentially life-saving treatment.” Likewise, people at risk for colon cancer can talk to their doctor about the best approaches—and frequency—for screening, he says. If someone who discovers they have a risk for a particular condition agrees to be contacted at a later date, and a relevant clinical trial becomes available, the project will let them know so they can choose whether or not to participate.
A person who has an identified genetic risk can also recommend genetic testing to their family members who may be at risk. “That's called ‘cascade testing’—it recognizes that if you have one of these risks, there's a 50-50 chance your siblings and your children have the same risk,” Dr. Murray says. “And almost certainly one of your parents had the same genetic risk variant and passed it on to you.”
Screening genes for medication sensitivity
In addition to determining risk for diseases, Generations performs pharmacogenomic screening, which provides information on sensitivity to certain medications.
“It's a limited number of genes and drugs that are involved, and most people are not on the drugs in question,” Dr. Murray says. The list includes medications used in the treatment of cancer and to prevent rejection after a kidney transplant, among others.
If the Generations screening shows a person will not do well on a particular medication—or might do best on a dose that is higher or lower than what is typically recommended—it’s valuable information to keep in a person's electronic health record. “If at some point a provider decides to prescribe that medication, an alert will pop up that will say something like, ‘This patient might need a different dose,’ or ‘This patient might need a different drug,’” Dr. Murray says.
One of the medications on the list is clopidogrel (the trade is name Plavix), which may be used in the emergency room for patients who have had a stroke or heart attack, so it would be useful for emergency room doctors to have that information at their fingertips [in a patient’s electronic health record], Dr. Murray says. “If you're having a heart attack and the provider wants to put you on that medication, they can't wait around for two or three days to get the results,” Dr. Murray says. “They need to know at that moment.”
Data is a boost for genetics research
In addition to the potential for individual good, Generations is being used to help improve knowledge for the greater population, says Dr. Murray. With that principle in mind, Generations can support qualified Yale researchers to link all of the DNA results to electronic health records to look for patterns in DNA that could be related to why some people do not get certain diseases. The data in Generations is anonymized and the work is under the oversight of a Yale Institutional Review Board that maintains a commitment to protecting the safety and interests of the volunteers.
Consistent with project goals, Generations is acting as a biorepository for the study of host genomic susceptibility to COVID-19, in an effort to understand if someone is predisposed to COVID-19 infection—or its severity.
Meanwhile, one advantage of the Generations biobank is that the New Haven area is diverse, so data collected here should be helpful for making connections between diseases and genes that can affect a variety of populations, Dr. Jiang says. “Diversity is important, because genetic susceptibility can be different among different races and ethnic groups,” he says. This could help not only with providing better treatments, but also with shaping national guidelines for screening for cancers and other diseases, he says. “There is a lot to learn; a lot to be investigated,” Dr. Jiang adds.
What if you get a positive result?
For those who are hesitant about genetic screening because they have concerns about keeping their information private, Dr. Murray says the Generations Project follows all the same guidelines as a hospital or doctor’s office. “We are operating inside of health care, so we follow all the rules and regulations of protection and management of your data—the same as if you went to the emergency room and were having some issue where it was important that you had privacy and protection of the information,” Dr. Murray says.
If you know your risk, you can be monitored or treated to prevent a bad outcome. Yong-Hu Jiang, MD, PhD, chief of Medical Genetics at Yale
People also should know that Generations screening results are not a diagnosis, he says. “It tells them if they are at risk for a particular disease,” says Dr. Murray, adding that the project should never be mistaken for an evaluation or replace a consultation with a doctor.
“If the idea of a health risk is frightening to somebody—or they want to wait—then they should wait, or talk to their friends or loved ones, or think about it or read about it,” he says. “We don't want anybody to join a project like this and regret doing it. So, we always make sure that people understand what they're signing up for. “
However, not knowing about a health risk won’t make the risk go away, Dr. Murray adds, and some people might have an invisible risk that they might never discover if they aren’t screened for it. “Knowledge is power—that’s what we hope people will get from this and value from it,” he says.
For more information or to enroll in the Generations Project, call 203-605-6884 or email firstname.lastname@example.org.