Everyone in a diverse, nearly 100,000-person sample carried at least one genetic variant that affects how their body processes medications, and a quarter of those people had been prescribed a medication that is known to be impacted by the variant they carried, a new University of Pittsburgh -led analysis reveals today in Science Translational Medicine .
The discovery highlights the value of genetic testing for some medications and that electronic health record alerts could be helpful when a clinician prescribes one of these medications. Such an alert would allow the clinician to consider prescribing an alternate medication or adjusting the dosage.
"Many people have experience with taking a medication that is not working well for them or that has a side effect," said senior author Philip E. Empey, Pharm.D., Ph.D. , associate professor in Pitt's School of Pharmacy and associate director for pharmacogenomics at the Institute for Precision Medicine at Pitt and UPMC . "While many things impact how a patient responds to medication, our research tells us that genetics could be factor for a large proportion of patients and it points to the value of precision medicine in prescribing."
More than 300 medications have information on their labels about genetic variant interactions, where genetic testing may be of value to guide prescribing, Empey said. One example is a chemotherapy drug used for colon cancer that could have serious toxicity in up to 8% of patients who carry these genetic variants, so those patients are proactively tested before treatment.
The research team used data from the National Institutes of Health (NIH) All of Us Research Program , an initiative that aims to gather data from 1 million people across the U.S. to help better understand how lifestyle, environment and genes influence health and disease. Pitt is a key partner in the program, launching All of Us Pennsylvania in 2018 .
The team evaluated the frequency of variants in 16 genes known to impact the effectiveness or toxicity of various medications among the participants. Everyone in the study was found to carry at least one such variant with a median of nine variants.
By then matching the genetic data to the participants' medical records, the research team also found that 24.4% had been prescribed at least one medication known to interact with a variant they carried. The most common medications identified in the review were ondansetron (anti-nausea), ibuprofen (anti-inflammatory), omeprazole and pantoprazole (both treat acid reflux and heartburn), and atorvastatin (lowers cholesterol).
The team also identified over 17,000 novel variants and reported the frequency of known medication-linked genetic variants across multiple ancestry groups, including in populations where these frequencies were not previously estimated.
"The limited diversity of racial and ethnic groups in early studies is a challenge in genetic research and skews risk estimates," Empey said. "That's part of the beauty of the All of Us Research Program – it was intentionally designed to help close these gaps by including people from a wide range of age groups, backgrounds and life experiences. It also underscores the value of having a large precision medicine dataset where whole genome testing data can be studied along with clinical data."
Empey said it will be up to policy makers and health insurers to weigh the benefits of widespread genetic screening for variants that interact with medications against the cost, and that this is a very active area of research. He said it makes sense to screen patients with a panel test that can look for common variants that are known to affect many medications and have these results in their medical record, much like a test for kidney function. This approach is also being applied in situations where patients are on many medications at the same time or in patients starting certain medications known to be impacted by genetics, such as clopidogrel, a medication used after cardiac stenting.
People who have already had this type of genetic screening, called pharmacogenomic testing, should be sure to share their results with their pharmacists and prescribers so that it is integrated with their electronic health record, Empey said. He is leading efforts at UPMC to make it easy for clinicians to see if a patient carries variants that may affect a medication that they're prescribing and recommend changes when needed.
"Just like with any new technology, it comes down to responsible implementation," Empey said. "Costs are coming down and the data is increasing, so it is important for patients and clinicians to be aware that the use of precision medicine in prescribing is becoming commonplace."
Additional authors on this research are Andrew Haddad, Pharm.D., Ph.D., and Kathleen Polkowski, Pharm.D., M.B.A., both of Pitt; Aparna Radhakrishnan, Ph.D., Sean McGee, Ph.D., Joshua D. Smith, Ph.D., Marsha M. Wheeler, Ph.D., Karynne Patterson, and Gail P. Jarvik, M.D., Ph.D., all of the University of Washington ; Jason H. Karnes, Pharm.D., Ph.D., of the University of Arizona ; Eric Venner, Ph.D., Kimberly Walker, M.S., Divya Kalra, M.S., Sara E. Kalla, Ph.D., Qiaoyan Wang, M.A., and Richard A. Gibbs, Ph.D., all of the Baylor College of Medicine ; and Janeth Sanchez, Ph.D., M.P.H., Anjené Musick, Ph.D., M.P.H., Andrea Ramirez, M.D., M.S., and Joshua C. Denny, M.D., M.S., on behalf of the All of Us Research Program.
This research was funded by the NIH (grants listed in the Science Translational Medicine manuscript), Shear Family Foundation and Myers Family Foundation .
