Pharmacogenomics and genetic ancestry: an opportunity to transform clinical practice in Colombia.

Pharmacogenomics has emerged as a clinically actionable discipline capable of reducing inter-individual variability in drug response, adverse drug reactions, and therapeutic failure. However, its real-world implementation remains constrained by a structural limitation: the predominance of Eurocentric genomic evidence and its limited clinical portability to genetically heterogeneous and underrepresented populations. This gap undermines the coherence between evidence generation, synthesis, and clinical application, particularly in admixed settings. Colombia represents a high-stakes case for pharmacogenomic implementation due to its marked inter-individual and regional genetic ancestry heterogeneity, coupled with a substantial and partly preventable burden of adverse drug reactions in an ageing and increasingly polypharmacy-exposed population. Direct extrapolation of pharmacogenomics panels and guidelines derived from other populations is therefore clinically risky and scientifically incoherent. In this Perspective, we propose an ancestry-based pharmacological diagnosis (APD) as a clinically oriented framework that integrates individual- and population-level genetic ancestry with actionable pharmacogenomics variants to inform drug selection, dosing, and risk stratification. APD is not a race-based or deterministic approach; rather, it treats ancestry as a probabilistic modifier of pharmacokinetic and pharmacodynamic variability, enhancing the external validity and clinical portability of pharmacogenomic guidance. We highlight CÓDIGO, a nationally led genomic consortium, as a proof-of-concept infrastructure enabling APD by providing ancestry-resolved allele frequencies and actionable variant data across Colombian populations. Finally, we discuss how APD can improve therapeutic efficacy, patient safety, health-system efficiency, equity, and scientific coherence, positioning ancestry-informed pharmacogenomics as a scalable and ethically grounded public-health strategy for precision medicine in Colombia and similar settings.