Nearly all Alabamians have genetic variations that could affect how they respond to medications for a range of conditions — from heart failure to cancer to depression. That is the conclusion of a new study based on data from the Alabama Genomic Health Initiative, one of the nation's first statewide efforts to harness the power of genomic analysis in clinical practice.One of the bedrock principles of precision medicine is the concept that a treatment that is optimal for one patient may not be best for the next. When it comes to drugs and genes, this research is called pharmacogenomics, or the study of how gene variation affects our response to medications.
The Clinical Pharmacogenetics Implementation Consortium (CPIC) and the Food and Drug Administration (FDA) review the evidence and determine gene/drug pairs where genetic information could be used to guide prescribing. But how often does pharmacogenetic information impact patients in the real world? How often are patients with actionable variants being prescribed drugs that may require a different dosage — or a different prescription altogether — based on their genetic makeup?
New study provides real-world data
A new study provides an answer for Alabamians. Based on analysis on 3,386 participants in the Alabama Genomic Health Initiative (AGHI), the paper by researchers at UAB and the HudsonAlpha Institute of Biotechnology in Huntsville says that "almost all Alabamians harbor at least one actionable genotype that can impact current or future medications, and a significant proportion are currently prescribed affected medications," they write.
The researchers found that 98.6% of those studied had actionable gene variants as designated by the CPIC. "Pharmacogenomics really has the potential to benefit everyone," said Brittney Davis, PharmD, first author on the article "Evaluation of population-level pharmacogenetic actionability in Alabama" and an instructor in the Department of Neurology's Program for Translational Pharmacogenomics.
"Pharmacogenomics really has the potential to benefit everyone," said Brittney Davis, PharmD, first author of the new study. Davis is an instructor in the Program for Translational Pharmacogenomics in the UAB Department of Neurology, where she is helping to embed gene-informed prescribing in clinical care.After earning an undergraduate degree in biology at UAB, Davis worked in cancer research at the university for four years after graduation. "I became really interested in how medications work and wanted to have a more direct impact on patient care, which led me to go to pharmacy school," she said. After graduating with her doctorate from Samford University in Birmingham, Davis recognized the promise of pharmacogenetics in personalizing medication therapy, and chose to pursue a fellowship with Nita Limdi, PharmD, Ph.D., director of UAB's Program for Translational Pharmacogenomics and co-principal investigator for AGHI. Limdi is the senior author on the new paper. "Pharmacogenomics is both intensely interesting and extremely impactful," Davis said.
The Alabama Genomic Health Initiative is one of the nation's first statewide efforts to harness the power of genomic analysis in helping identify those who are at risk for diseases caused by genomic abnormalities.
AGHI has enrolled more than 7,000 participants from all 67 Alabama counties since it launched in 2017. Participants receive genomic testing, interpretation and counseling free of charge. “AGHI is designed to advance scientific understanding of the role that genes play in health and disease,” said Bruce Korf, M.D., Ph.D., associate dean for Genomic Medicine, UAB Chief Genomics Officer and AGHI’s principal investigator.
Most previous pharmacogenomic studies have been based on patient data from academic medical centers, Davis notes. "Enabled by AGHI, our study is the first of its kind to examine the question at a statewide level," she said.
Results ‘differed significantly by race’
In their new paper, the researchers also noted that "the prevalence of actionable genotypes by gene differed significantly by race." These racial differences were particularly notable in participants prescribed the beta blockers atenolol, carvedilol and metoprolol, commonly used to manage heart failure. Overall, about 50% of participants studied had an actionable variant in the ADRB1 gene, which is associated with decreased therapeutic response to beta blockers. For Black participants, that rate was 62.5%, while it was 47.4% for white participants.
Top genes based on prescribing
Among AGHI participants currently taking prescription medications, a significant number were prescribed medications affected by pharmacogenetic variation in these genes:
- CYP2D6 – 70.9%
- G6PD – 54.1%
- CYP2C19 – 53.5%
- CYP2C9 – 47.5%
Unlike many studies, the AGHI cohort includes a racially diverse population, with 18% of participants self-reporting as Black. "Here we show that pharmacogenetics is actionable for all Alabamians, independent of their race," Limdi said.
Embedding pharmacogenomics in clinical care
Korf says the AGHI is now entering a new phase, which he calls AGHI (2.0), that “will focus on enrollment in primary care clinics in an effort to integrate genomics in routine medical care,” he said. In addition to reports on genetic disease risk, participants and their health care providers now are receiving pharmacogenomic information, which will be included in the participants' electronic medical records (EMR). “The return of pharmacogenetic information and its integration into our EMR is being led by pharmacists specializing in pharmacogenomics,” Korf said. “Drs. Davis and Limdi are leading this effort, embedding pharmacogenomics in clinical care.”
“I am very excited to be a part of a field that will change how people around our state and around the world receive care," said Davis, who will help return pharmacogenetic results to patients as part of AGHI.
"This is where the action is in precision medicine," Limdi said. "We are laying the foundation on how to integrate genomic medicine in clinical care. Pharmacogenomics is poised to affect both individuals and the population at large."
A sampling of gene/drug pairs where genetic information can be used to guide prescribing, along with the condition treated by that drug.
