<p>Inconsistency in race and ethnic classification in pharmacogenetics studies and its potential clinical implications</p>

Abstract

Introduction Racial and ethnic categories are frequently used in pharmacogenetics literature to stratify patients; however, these categories can be inconsistent across different studies. To address the ongoing debate on the applicability of traditional concepts of race and ethnicity in the context of precision medicine, we aimed to review the application of current racial and ethnic categories in pharmacogenetics and its potential impact on clinical care. Methods One hundred and three total pharmacogenetics papers involving the CYP2C9, CYP2C19 , and CYP2D6 genes were analyzed for their country of origin, racial, and ethnic categories used, and allele frequency data. Correspondence between the major continental racial categories promulgated by National Institutes of Health (NIH) and those reported by the pharmacogenetics papers was evaluated. Results The racial and ethnic categories used in the papers we analyzed were highly heterogeneous. In total, we found 66 different racial and ethnic categories used which fall under the NIH race category “White”, 47 different racial and ethnic categories for “Asian”, and 62 different categories for “Black”. The number of categories used varied widely based on country of origin: Japan used the highest number of different categories for “White” with 17, Malaysia used the highest number for “Asian” with 24, and the US used the highest number for “Black” with 28. Significant variation in allele frequency between different ethnic subgroups was identified within 3 major continental racial categories. Conclusion Our analysis showed that racial and ethnic classification is highly inconsistent across different papers as well as between different countries. Evidence-based consensus is necessary for optimal use of self-identified race as well as geographical ancestry in pharmacogenetics. Common taxonomy of geographical ancestry which reflects specifics of particular countries and is accepted by the entire scientific community can facilitate reproducible pharmacogenetic research and clinical implementation of its results.

Meta-analysis of probability estimates of worldwide variation of CYP2D6 and CYP2C19

“…Although grouping populations can simplify reporting of pharmacogenetic alleles, we grouped ethnicities within geographical regions to enable comparisons with other published meta-analyses 71 , 72 . The prevalences of our CYP2D6 predicted phenotypes were in general agreement with those reported by Gaedigk et al 17 .…”

PharmVar GeneFocus: CYP2C19

“…Phenotype frequencies across populations are provided in the “Calculated phenotype frequency” tab in the PharmGKB/CPIC CYP2C19 Frequency Table 44 . We stress, however, to view all phenotype group frequencies (including those shown in the PharmGKB/CPIC table) with caution due to the limitations regarding the accuracy of allele frequencies, as well as the method used to translate genotype into phenotype and inconsistencies in the classification of “population,” “ethnicity,” or “race.” 77 …”

Genotype‐guided warfarin therapy: Still of only questionable value two decades on

“…However, this raises an issue concerning the determination of the race/ethnicity of a patient. Racial and ethnic classification is highly inconsistent across different studies as well as between different countries and there is a clear need for evidence‐based consensus for optimal use of self‐identified race as well as geographical ancestry in pharmacogenetics . Self‐identified ethnicity and skin colour have been reported to be poor indicators of genetic ancestry .…”