Precision medicine: does ethnicity information complement genotype-based prescribing decisions?

Abstract

Inter-ethnic differences in drug response are all too well known. These are underpinned by a number of factors, including pharmacogenetic differences across various ethnic populations. Precision medicine relies on genotype-based prescribing decisions with the aim of maximizing efficacy and mitigating the risks. When there is no access to genotyping tests, ethnicity is frequently regarded as a proxy of the patient’s probable genotype on the basis of overall population-based frequency of genetic variations in the ethnic group the patient belongs to, with some variations being ethnicity-specific. However, ever-increasing transcontinental migration of populations and the resulting admixing of populations have undermined the utility of self-identified ethnicity in predicting the genetic ancestry, and therefore the genotype, of the patient. An example of the relevance of genetic ancestry of a patient is the inadequate performance of European-derived pharmacogenetic dosing algorithms of warfarin in African Americans, Brazilians and Caribbean Hispanics. Consequently, genotyping a patient potentially requires testing for all known clinically actionable variants that the patient may harbour, and new variants that are likely to be identified using state-of the art next-generation sequencing-based methods. Furthermore, self-identified ethnicity is associated with a number of ethnicity-related attributes and non-genetic factors that potentially influence the risk of phenoconversion (genotype–phenotype discordance), which may adversely impact the success of genotype-based prescribing decisions. Therefore, while genotype-based prescribing decisions are important in implementing precision medicine, ethnicity should not be disregarded.