All of Us study finds thousands of new drug-response genetic variants
An analysis of nearly 100,000 diverse participants in the NIH's All of Us program revealed thousands of new genetic variants in pharmacogenes.
A new analysis of the All of Us program has identified thousands of previously unknown genetic variants that affect how people respond to prescription drugs. The study of nearly 100,000 U.S. residents found every participant carried at least one variant in 16 key pharmacogenes, and about one in four had taken a medication potentially impacted by these genetic differences.
Scientists used data from the U.S. National Institutes of Health's All of Us program, which aims to collect genetic data from 1 million Americans from diverse backgrounds. The work analyzed genes associated with drug metabolism. Variants in these pharmacogenes can alter how the body processes medications, potentially requiring dose adjustments, intensifying side effects, or rendering a drug ineffective. The affected drugs include selective serotonin reuptake inhibitors, statins, chemotherapy agents, and the blood thinner Plavix.
Diversity expands the scope of discovery
The study's diverse cohort enabled discoveries that narrower databases missed. The broader representation of different racial and ethnic groups allowed researchers to identify genetic variants not previously cataloged in other large genomic resources like the U.K. Biobank. This shows the value of inclusive research for comprehensive medical genetics. Loren Saulsberry, a health policy researcher, said, "This really furthers the emerging evidence of how genetically guided clinical care adds benefit across a diverse population."
Having a dataset that reflects the broader population will help limit disparities in health outcomes as pharmacogenomic findings are translated into clinical practice. The paper highlights the need for greater clinical attention to genetics, as many people are not genomically sequenced and physicians may be unaware of how genetic variants influence the drugs they prescribe.
Funding pressures threaten the program's future
This advance comes as the All of Us program faces severe financial constraints. Funding from the 21st Century Cures Act will end in fiscal year 2027, and Congress is currently operating under a temporary budget. Once a final budget is passed, the program expects to receive $122 million-an 80% drop from its peak funding in 2023.
The cuts have already forced dramatic rollbacks. Engagement activities and enrollment at academic medical centers, federally qualified health centers, and mobile units have been scaled back. Critically, the program has stopped offering participants their individual genetic testing results due to funding concerns. These reductions jeopardize the long-term goal of building a robust dataset for precision health.
The program began recruiting children in 2023, and around 5,000 are currently enrolled, though their data is not yet available to researchers. Sara Van Driest, director of pediatrics for All of Us, emphasized that stable and increased funding is essential to enroll children at scale and build the dataset needed for the future of precision health. Philip Empey of the University of Pittsburgh, senior author on the paper, and former All of Us CEO Joshua Denny have been involved in the work, which points to genetics as one key factor explaining differences in patient drug responses.
