Empirical Drug Dosage Validates Pharmacogenomic Associations in All of Us

The All of Us research program, a national longitudinal study conducted by the US National Institutes of Health, provides robust medical history, drug dosage and genomic data from a diverse population. All of Us offers an opportunity to discover novel correlations between drug dosage and genetic variation. However, first it is necessary to evaluate the quality and quantity of the data and its ability to replicate known associations. In this paper, we investigate whether known drug-gene interactions can be recovered from the All of Us dataset, based on data from electronic health records. Focusing on the Cytochrome P450 (CYP450) enzyme family, which metabolizes approximately 90% of clinically available drugs, we evaluate 61 drugs metabolized by the enzymes. We then identify significant differences in drug dosages across CYP450 metabolizer phenotypes. Our results validate some known interactors of CYP2D6, CYP2C19, CYP2C9, and CYP3A5. However, we did not recover all validated PGx interactions, potentially due to noise, lack of doctors adjusting drug dosage or phenoconversion. Nevertheless, our findings highlight the potential of the All of Us dataset, which captures some known pharmacogenomic interactions.