TY  - JOUR
T1  - Ancestry Labels Are Poor Substitutes for Functional Pharmacogenomic Evidence
A1  - Daniel Kim
A1  - Jihoon Park
A1  - Min-seo Kang
A1  - Hyun-woo Jung
JF  - International Journal of Pharmaceutical Research and Allied Sciences
JO  - Int J Pharm Res Allied Sci
SN  - 2277-3657
Y1  - 2025
VL  - 14
IS  - 3
DO  - 10.51847/BW31g5lSWH
SP  - 152
EP  - 161
N2  - Pharmacogenomics aims to improve drug selection and dosing by identifying biological sources of interindividual variability in pharmacokinetics, pharmacodynamics, toxicity, and treatment response. Population ancestry can contribute useful information because pharmacogene allele frequencies and haplotype structures differ across human populations. Yet ancestry labels operate at a fundamentally different evidentiary level from an individual patient’s functional pharmacogenomic state. Broad racial, ethnic, continental, or biogeographic categories compress substantial within-population diversity, perform particularly poorly in admixed individuals, and cannot determine whether a detected variant alters protein function, exposure, or drug response. Their limitations are amplified when genotyping panels incompletely represent population diversity or when environmental and clinical factors modify genotype-predicted phenotypes. This Current Opinion argues that ancestry should be retained as contextual information for discovery, representation assessment, assay design, and population-level uncertainty, but should not be treated as a functional biomarker. The clinically relevant evidentiary progression is instead from accurate variant and haplotype ascertainment, through experimentally or clinically supported functional interpretation, to drug-specific phenotype and actionability assessment. A proposed evidence hierarchy is developed in which ancestry informs where uncertainty should be investigated, whereas direct genomic, functional, pharmacological, and clinical evidence determines what should be acted upon. This distinction can improve both scientific precision and equity by avoiding two opposite errors: ignoring population genetic structure and converting population membership into an assumed individual biological phenotype.
UR  - https://ijpras.com/article/ancestry-labels-are-poor-substitutes-for-functional-pharmacogenomic-evidence-pd9pjn6exnxrfgc
ER  -