All of Us study finds thousands of new genetic variants affecting drug responses

“If you have a prior experience with a medicine that did not work for you, or had a side effect, we can’t say it’s absolutely because of genetics, but we are appreciating more and more that people are different, and genetics is one reason that may suggest where there may be differences,” said Philip Empey, who directs the Center for Clinical Pharmaceutical Sciences at the University of Pittsburgh and was the senior author on the paper.

The paper points to the need to give more attention to the role genetics plays in the clinic, Empey added. But there are a number of barriers before these results can make their way into patient care. Many people don’t have their genomes sequenced, physicians may not be aware of how drugs they are prescribing are affected by genetic variants, and there are a constellation of variants that could impact drugs.

The All of Us Research Program has the goal of collecting genetic data from 1 million Americans from diverse backgrounds. That diversity helped identify variants not found in previous work using other genomic databases like the U.K. Biobank.

Part of the concern with new technologies is that they may not be as effective for marginalized populations, but having such a diverse dataset to start with will help limit disparities in outcomes as the findings are translated into clinical use, Saulsberry said.

The potential benefits of All of Us’s data going forward may be affected by funding woes. The program is supported by two sources: the 21st Century Cures Act, enacted in 2016, and yearly appropriations from Congress. That former avenue will dry up in the 2027 fiscal year. Congress is currently operating under a temporary budget, called a continuing resolution, but the program expects to receive $122 million in funding once a budget is finalized, an 80% drop from its peak in 2023.

Those cuts have meant that All of Us has had to be less ambitious in its recruiting of patients, said Joshua Denny, who was CEO of the program until the end of October and is now in a leadership position at the University of Chicago. “The engagement activities, the brick and mortar that we had enrolling at academic medical centers and FQHCs and mobile units. These kinds of things … were cut back dramatically,” he said. The program has also stopped offering participants the ability to see the results of their genetic testing because of funding concerns.

Another area where All of Us has had to temper its aims has been with recruiting children, which it began in 2023. At this point, it has around 5,000 children enrolled in the study but those data are not yet available to researchers, said Sara Van Driest, director of pediatrics for All of Us.

“In order to really enroll children at scale and build a dataset that’s going to fuel the future of precision health, we’re going to need stable funding in the years ahead,” she added. “I should say, increased and stable funding in the years ahead.”