As it moves forward with plans to fully sequence the genomes of at least 1 million people across the U.S., the National Institutes of Health's (NIH's) All of Us study is changing the research paradigm.
As promised, the All of Us research program has begun returning personalized health-related DNA results to participants, marking the largest-scale effort to date to share hereditary disease risk and pharmacogenetic information with study participants, according to NIH officials.
By returning health-related DNA information to participants, NIH is turning research into a "two-way street—fueling both scientific and personal discovery that could help individuals navigate their own health,” said Josh Denny, M.D., CEO of the All of Us program.
“This type of partnership with our participants is crucial for building trust and fulfilling the commitment we made to drive research that can offer meaningful insights for all.”
When the NIH announced the All of Us initiative in 2015, it kicked off the largest health and medical research program on precision medicine with the goal of collecting health data on 1 million people.
The program is now halfway to its recruitment goal with more than 500,000 participants enrolled. All of Us opened for enrollment in May 2018 and currently enrolls participants 18 years of age or older from a network of more than 340 recruitment sites.
More than 240,000 participants have signaled their interest in receiving the DNA results from the program. The new reports detail whether participants have an increased risk for specific health conditions and how their body might process certain medications.
"It's going to be really exciting to be able to have information out there for researchers to be able to look at the genetic data and combine that with the electronic health records and then use all of this information to be able to conduct studies around precision medicine and to being able to understand how this data could be used to be able to improve health for all of us," Anastasia Wise, Ph.D., director for scientific return to participants and impact at the All of Us program, said.
She noted that the All of Us research program has been developed with feedback and engagement from participants. "They've been a part of the process from the beginning to be able to help inform the development of these results. We've tested them with participants to make sure that the results are going to be understandable, easy to use and inclusive," she said. "We hope that this is going to be an iterative process over time and that our participants will continue to help us build this program."
Currently, there are 155,0000 participants who provided a blood sample and consented to receive genomic information who are eligible to receive their health-related DNA results. More than 4,000 study participants have viewed their results, according to Wise.
The program’s Hereditary Disease Risk report, informed by recommendations from the American College of Medical Genetics and Genomics, includes 59 genes and variants that are associated with serious, medically actionable health conditions. These genes are linked with an increased risk of specific cancers, heart conditions, blood disorders and more. The program anticipates that 2% to 3% of participants will receive a result showing a pathogenic or likely pathogenic variant linked in one of the genes included in the report.
Participants can also choose to receive a report that includes seven genes that are known to affect how the body processes certain medicines.
The program started returning genetic ancestry and trait results to participants in December 2020. So far, the program has offered genetic ancestry and traits results to more than 175,000 participants and continues to return about 6,000 results each month.
The program plans to increase the number of participants who are invited to receive genetic health-related results throughout 2023, including new participants who join the program.
"I think one of the interesting things about the All of Us research program is from Day One, they've always thought of participants as partners," said Alicia Zhou, Ph.D., chief science officer at health tech company Color Health. "In addition to generating this really valuable and useful data asset for the research community, which will definitely accelerate the pace of medicine discovery, there's also this component of returning results back to participants and making sure that the participants themselves are also receiving value out of them."
She added, "All of Us is setting a new precedent for longitudinal research programs."
In 2019, NIH tapped Color to serve as the genetic counseling resource for the All of Us program. Study participants who choose to get health-related DNA results can schedule a meeting with a genetic counselor to review and discuss their findings.
The deal included a $4.6 million award.
Color launched in 2015 with a focus on gene testing and precision genomics. The company has since expanded its capabilities to focus on improving key health infrastructure systems across the U.S.—including those related to the “last mile” delivery of COVID-19 vaccines.
The NIH is tapping into Color's genomics services as part of the partnership. The company assists with clinical validation of the DNA samples. "We are the clinical validation lab for one of the genome centers at the Broad Institute. We also help do the report harmonization across all the genome centers to make sure that every participant in the program has a similar-looking report, regardless of where it was processed at one genome center or another. And then we deliver the genetic counseling back to participants," Zhou said.
"Color also powers the digital infrastructure for the overall process of returning genetic results to study participants," she noted.
The key is to provide patients with "actionable results" to better understand their health and potential genetic risks.
If a study participant's DNA results show they may have an increased risk of a serious health condition, they can opt to get a clinical DNA test through the program’s genetic counseling resource. Color runs the free clinical DNA tests.
But what are the next steps? There's been a lot of discussion about incorporating genetics and DNA screening into primary care practices, but most providers lag behind.
Many primary care providers feel largely unprepared to discuss the implications of genetic testing with their patients.
"This is actually something that, at the program, we've thought quite a lot about," Zhou said. "We developed educational materials, not just for our participants, but also for providers, because we imagine that some healthcare providers might be very familiar with this information, and others might find this very novel. We've actually been thinking about all of the different sorts of audiences that might be interacting with these results and ensuring that we have the right kind of materials developed for everyone."
The genetic counseling service also serves as a resource that's available to providers, Wise noted. "Providers can also reach out to a genetic counselor and ask, 'What are these results? How might I pursue next steps to be able to follow up with this participant?'"
All of Us aims to partner with at least 1 million people who reflect the diversity of the U.S. to accelerate medical breakthroughs. About 80% of All of Us participants represent communities that have been historically underrepresented in medical research, and nearly 50% of All of Us participants identify with a racial or ethnic minority group.
Most large genetic databases have historically gathered DNA information from largely European and Caucasian people. "The idea here with the All of Us research program is to recruit from not only ethnically diverse populations, but also age diversity, socioeconomic status, gender identity, rural versus urban populations, really trying to ensure that the work that's being done and the research that gets accelerated by this type of access to data, that it will be more equitable across all populations compared to what's been done in the past," Zhou said.