The Outlier in All of Us: Why Implementing Pharmacogenomics Could Matter for Everyone

Abstract

The field of pharmacogenomics originally emerged in the 1950s from observations that a few rare individuals had unexpected, severe reactions to drugs. 1 As recently as just 6 years ago, prominent views on the subject had largely remained unchanged, with authors from the US Food and Drug Administration (FDA) citing the purpose of pharmacogenetics as “tailoring treatment for the outliers.” 2 It should not be surprising if this is the prevailing view—the best‐studied pharmacogenomic drug examples are indeed just that, genetic explanations of extreme responses or susceptibilities among usually a very small fraction of the human population. Thiopurine methyltransferase (TPMT) deficiency as a cause of severe myelosuppression upon treatment with azathioprine or mercaptopurine is found as a heterozygous trait in only ∼10% of patients, and homozygous (deficiency) carriers are even more rare—occurring in fewer than 1 in 300 patients. 3, 4 Malignant hyperthermia resulting from inhaled anesthetics and succinylcholine is believed to have a genetic incidence of only about 1 in 2000 people. 5