A US government study that aims to sequence the genomes of 1 million volunteers will partner with a genetic-counselling company to help participants understand their results. It will be the largest US government study to provide such a service.

The National Institutes of Health (NIH), which is leading the project — called All of Us — announced the US$4.6 million, five-year grant to the counselling and health technology company Color on 21 August.

The firm, in Burlingame, California, will counsel every participant with a genetic variant that could have serious health implications — such as the BRCA gene associated with breast cancer — when they receive their results. Color will also develop educational materials for all study participants, and will offer telephone consultations to any who wish to discuss their genetic test results with a counsellor.

“This is a really responsible and more equitable way of communicating the results of research to all participants,” says Bartha Knoppers, the director of genomics and policy at McGill University in Montreal, Canada. “They’re laying the foundations for building good bridges between the findings and the people.”

Prioritizing inclusion

The All of Us study, which launched in May 2018, aims to enrol at least 1 million people. Participants will be asked to volunteer a host of health information, including electronic health records, genomic data and blood and urine samples. Study researchers also plan to collect data recorded by personal activity trackers, such as those found on smartphones. They will store the data in an online database that outside scientists can access with permission from the programme.

Enrolling participants from ethnic and socio-economic groups that are typically under-represented in biomedical research is a priority for the study's organizers. Most genomic research to date has been conducted on non-Hispanic white people. One recent review ¹ in the New England Journal of Medicine found that as of 2018, 78% of people included in genomic studies of disease were of European descent. That bias narrows the applicability of genetic testing, and can lead to misleading or dangerous interpretations of genetic variants from non-white populations.

The All of Us study has enrolled 175,000 people around the country. About 50% are non-white, and 80% are from groups that have historically been under-represented in biomedical research.

But to generate the kind of long-term data set necessary for breakthroughs in precision medicine — which uses genomic, physiological or other data to tailor treatments to individuals — All of Us must retain these enrolees, ideally over the course of their lives. That’s where genetic counselling comes in.

“It’s imperative to our mission that we return value to our participants, that we communicate back the results of [our] research,” says Stephanie Devaney, the deputy director of All of Us, in Bethesda, Maryland.

Working out the details

This is a step in the right direction, says Amy McGuire, a bioethicist at Baylor University in Waco, Texas. But “the devil is in the details”, she adds.

And Devaney and her colleagues still need to work out a lot of details — including exactly what kinds of information the programme will give participants about their own genomes, and how. A genetic counsellor will give people information on genetic variants that have clear, actionable consequences for health, such as the BRCA gene. But Devaney says that study organizers are still discussing how much to tell participants about genetic variants that don’t have as explicit a link to illness.

Their task is complicated by the fact that knowledge about genetic variants can change over time. A mutation that researchers now think is benign could someday be considered an indication of an increased cancer risk. All of Us participants are told that their genetic test results could change as scientists learn more about certain mutations, says Brad Ozenberger, genomics program director for All of Us. But he and his colleagues are still working out how frequently to notify participants of such developments.

What a genetic variant means for someone can also depend on their ethnicity . Certain genetic tests that physicians use to help determine whether someone with cancer should undergo chemotherapy have only been tested in white Europeans. It's unclear whether the test is accurate for non-white people. All of Us and Color say that they are figuring out the best way to communicate these uncertainties to study participants.

The company says that it’s prepared to have those conversations. “We’ve worked with a lot of diverse communities,” says Alicia Zhou, vice president of research and scientific affairs at Color. They include technology and manufacturing companies, railroad workers in Alaska and residents of Trinidad and Tobago, she adds.