All people carry differences in their DNA that could affect how they respond to medication, according to my team’s newly published research. Moreover, 1 in 4 already take a medication their body processes differently because of their genetics.
Clinicians often take a trial and error approach to prescriptions. Two people take the same medicine at the same dose. One starts feeling better, but the other experiences side effects or sees little benefit. For some medications, part of the reason behind that difference in response is written in a person’s DNA.
The field of pharmacogenomics studies how variations in your DNA contribute to how your body processes and responds to medicines. For instance, genes can influence how quickly your liver breaks down a drug and how long it stays in your bloodstream.
But using genetic testing to guide prescriptions is not yet routine. Part of the problem is a lack of large population data to study this approach more broadly. Clinicians don’t know when it’s best to order genetic testing. And because most genetic research has been done on people of European ancestry, researchers know less about how common key gene variants are in everyone else.
Genetic variants and drugs
To improve the diversity of pharmacogenomic data, my team of researchers and I analyzed the whole genome sequences and health records of nearly 100,000 participants in the All of Us Research Program. All of Us is an effort from the National Institutes of Health to study the health of 1 million or more people across the U.S. and its territories, with a focus on groups historically left out of biomedical research.
We examined 16 genes with well-established links to how someone responds to different medications, pairing this data with electronic health records to identify which drugs participants had already taken.
We found that every participant carried at least one relevant genetic variant, and many carried several. Around 99.5% of participants had a genetic variant for which the Food and Drug Administration or medical guidelines recommend a different drug or change in dose for certain medications.
Even more telling, about 24% had taken a drug that is affected by a genetic variant they carried. Common examples included drugs used to reduce excess stomach acid, such as omeprazole and pantoprazole, and statins used to lower cholesterol levels. Because health records can be incomplete, our results likely underestimate the actual prevalence of these gene-drug interactions.
These findings can help improve the databases clinicians and researchers use routinely in research. We identified 17,704 previously unreported variants in the regions of these genes that encode proteins. Computer models predicted that about a quarter may have significant effects on how the body processes drugs.
Our team also reported the frequencies of hundreds of genetic variants linked to drug response for people from genetic ancestries that previously had incomplete data.
Improving precision medicine
Overall, our research shows that DNA variation is very common, and broader genetic testing may help optimize the medications clinicians prescribe to patients. It’s also an example of how big initiatives such as the All of Us Research Program can advance precision medicine.
However, this study doesn’t prove testing would improve outcomes for each of these people. Additionally, genes are only one factor; age, kidney and liver function, and other medications also affect how the body processes drugs.
Still, I believe the direction of the research is clear. Pharmacogenomics can provide potentially relevant benefits for many people who take medications.
Philip Empey receives funding from the NIH, Veterans Administration, Shear Family Foundation and Myers Family Foundation.
