P418: A genome sequencing approach to pharmacogenomic profiling across diverse population in a large health system

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Genetics in Medicine Open


washington; renton; genomics



Due to the variability in drug efficacy and safety attributed to an individual’s genetic profile, pharmacogenomics (PGx) is rapidly becoming a cornerstone of precision medicine. PGx testing has traditionally been conducted through selected gene panels with pre-defined variants. Through the Genomic Medicine for Everyone (Geno4ME) program, we piloted PGx using a genome sequencing method in the highly diverse seven-state Providence Health System.


Geno4ME provides genetic population health screening to Providence patients with return of clinically actionable results. For this PGx study, we developed and validated a pilot gene-drug panel using genome sequencing. We utilized Clinical Pharmacogenetics Implementation Consortium (CPIC®) and FDA guides combined with the highest prescription usage data across all regions and races/ethnicities in our health system to select the following seven gene-drug pairs: CYP2C19 for two selective serotonin reuptake inhibitors (SSRIs), three proton pump inhibitors (PPIs), and one antiplatelet, clopidogrel, as well as CYP2C9, CYP4F2, VKORC1, and rs12777823 for one anticoagulant, warfarin. As part of Geno4ME return of results, PGx report was shared with each enrolled individual and their designated provider via the Electronic Health Record (EHR). PGx pharmacist consultation was provided to individuals who had a positive and actionable result. A personalized medication action plan including educational resources was shared with providers and individuals for therapy optimization when warranted upon clinical evaluation.


Between March 2021 to October 2022, 2,111 individuals were consented to the Geno4ME program, 1,247 had results returned, and all had at least one PGx recommendation based on their genotype alone. Of these, 174/1,247 (14%) screened positive for gene-drug interaction(s) for one or more drugs being taken at time of enrollment. After chart review and consultation with pharmacist, 68/174 (39%) of the gene-drug cases were both positive and actionable, ie, the individual was still on the associated drug and had met the CPIC guideline specified diagnosis at the time of outreach. We determined 41/68 (60%) did not warrant medication adjustment as these individuals were already on the lowest effective dose without clinical risk factors (eg, diagnosis of osteoporosis, history of falls, or drug-drug interactions) or dose adjustment had already been made at the time of outreach. The remaining 27/68 (40%) resulted in medication interventions including dose adjustment, therapy alternatives, or prevention of drug-drug-gene interaction. 74% of therapy changes were for PPIs, 22% SSRIs, and 4% antiplatelet. Overall, this high-touch PGx pharmacist intervention led to 84% provider acceptance to therapy recommendation, and 74% individuals with successful clinical outcomes after at least 3 months of therapy change. Additionally, we identified two rare cases of CYP4F2 whole gene deletion (not reported in PharmVar) in individuals of East Asian ancestry as well as two cases of partial CYP2C19 gene deletion (CYP2C19*37) in individuals of European ancestry.


This pilot demonstrated initial strong engagement in PGx utilization by providers and patients in a community-based health system as the result of high-touch clinical support and targeted high impact gene-drug selection. Use of genome sequencing, which allows data reanalysis and detection of more variants in an ethnically diverse setting, makes this sequencing method a better platform for population PGx. In this pilot 100% of the study individuals had PGx genetic data that can guide treatment decisions at some point of their care continuum. Given the high percentage of positive cases and the dynamic nature of medication use, an automated system with a clinical decision support tool that integrates discrete genomic content into the EHR is key to scale up PGx implementation. Additionally, providing clinicians easy access to effective educational resources and clinical support is essential to improve PGx real-time actionability and enable meaningful adoption as standard of care.