Longevity
Gene study in 100,000 Americans finds drug-response variants missed by earlier research
By Alaethia Blech, . Life and Health Today.
Every participant in a study of nearly 100,000 Americans carried at least one variant in a set of genes that govern how the body handles prescription drugs, researchers reported in the journal Science Translational Medicine. One in four of those participants had also taken a medication directly affected by such variants, according to the paper, which drew on data from the National Institutes of Health's All of Us Research Program.
What pharmacogenes are and why they matter
Pharmacogenes are genes that influence how a person metabolizes, or breaks down, a drug. Variants in these genes can mean a standard dose moves through the body too quickly or too slowly, producing side effects that would not appear in someone without the variant, or leaving the drug too weak to work at all. The 16 pharmacogenes examined in this study affect how the body handles a wide range of medications, including selective serotonin reuptake inhibitors (a common class of antidepressants), statins (cholesterol-lowering drugs), certain chemotherapy agents, and the blood thinner clopidogrel, sold under the brand name Plavix, according to STAT News.
Philip Empey, who directs the Center for Clinical Pharmaceutical Sciences at the University of Pittsburgh and was the paper's senior author, told STAT: "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."
Why diversity in the dataset changes what gets found
Previous large genomic databases, including the U.K. Biobank, have skewed heavily toward participants of European ancestry. All of Us was designed to recruit broadly across racial, ethnic and socioeconomic backgrounds, and that breadth is what allowed the researchers to surface thousands of variants that earlier work had not captured. Loren Saulsberry, a health policy researcher who studies equity in pharmacogenomics and was not involved in the paper, told STAT that starting with a diverse dataset should help limit disparities in outcomes as the findings move toward clinical use.
The PubMed abstract for the paper adds that nearly all participants, 99.13 percent, had a predicted phenotype, meaning a genetically anticipated drug-response profile, that carries prescribing recommendations under existing clinical guidelines.
What stands between this finding and a changed prescription
Empey told STAT that several barriers remain before results like these reach patients. Genome sequencing is not routine in clinical care. Many physicians are not trained to interpret how genetic variants interact with the drugs they prescribe. And the number of variants that could affect any given drug is large enough to make interpretation complex.
The All of Us program itself faces a funding squeeze that could slow the work. STAT News reported that the program's budget is expected to fall to $122 million once Congress finalizes a budget, an 80 percent drop from its peak in 2023. The 21st Century Cures Act, one of the program's two funding sources, will stop providing money in the 2027 fiscal year. Joshua Denny, who served as the program's chief executive until the end of October and has since moved to a leadership role at the University of Chicago, told STAT that enrollment activities at academic medical centers, federally qualified health centers and mobile units "were cut back dramatically." The program has also suspended offering participants access to their own genetic results because of the funding situation, STAT News reported.
A pediatric arm of All of Us enrolled around 5,000 children beginning in 2023, but Sara Van Driest, the program's director of pediatrics, told STAT those data are not yet available to researchers. "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 said.
What this means for a reader thinking about their own medications
This study measures how common pharmacogenomic variants are across a diverse population and how often those variants overlap with actual drug use. It was not designed to show that genetically guided prescribing produces better outcomes in the people studied, and it does not establish that. What it does establish is that the genetic variation is widespread, that it touches drugs many people already take, and that earlier research underestimated it by working from less diverse populations.
Whether any of this is relevant to an individual's own prescriptions is a question for a clinician who knows their full medical history. Routine pharmacogenomic testing is not yet standard care, and the gap between a published finding and a changed prescription remains wide.
Life & Health Today provides information for educational purposes only, not medical advice, diagnosis, or treatment. Always consult a qualified healthcare professional.