{"doi":"10.3389/fphar.2025.1636451","title":"Pharmacogenomics and genetic ancestry in Colombia: a study on all variant drug annotations of PharmGKB","abstract":"<jats:sec><jats:title>Background</jats:title><jats:p>To generate an ancestry-resolved pharmacogenomic (PGx) landscape for Colombia by integrating all PharmGKB variant-drug annotations with local allele-frequency data, thereby quantifying inter-ancestry differences of clinical relevance and exposing evidence gaps that hinder equitable precision medicine.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We conducted a cross-sectional analysis of 4,462 PharmGKB variant annotations (1994–2024), retaining 1,216 significant single-nucleotide polymorphisms (SNPs) reported in 552 studies. Allele frequencies were extracted for five Colombian populations: two predominantly African (Palenque [PLQ], Chocó [CHG]) and three predominantly European (ATQCES, ATQPGC, CLM), from the CÓDIGO database. Spearman correlations compared population-specific PGx profiles; SNPs with &amp;gt;25 percentage-point frequency differentials were tabulated.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>European ancestry dominated the global evidence base, representing 51.5% of 651,532 participants, while African ancestry accounted for only 0.46% (n = 3,031). Strong correlations were observed among European-leaning Antioquians (<jats:italic>r</jats:italic><jats:sup>2</jats:sup> ≥ 0.90), whereas PLQ exhibited inverse or negligible correlations with those groups (<jats:italic>r</jats:italic><jats:sup>2</jats:sup> = −0.20 to −0.02) and minimal similarity with CHG (<jats:italic>r</jats:italic><jats:sup>2</jats:sup> = 0.12). Twenty-eight SNPs were frequent in PLQ (&amp;gt;75%) but rare in Europeans (&amp;lt;50%), and 44 showed the opposite pattern. Notable examples include CYP3A4 rs3735451-C (rivaroxaban; 87.1% vs. 23.2%), CYP3A5 rs776746-T (tacrolimus; 85% vs. 23.5%), and rs55881666-C (duloxetine; 15% vs. 84%). Globally, 71.5% of PGx studies originated in high-income countries.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Large, clinically actionable allele-frequency contrasts and pronounced discovery biases confirm the need for ancestry-aware PGx testing and locally calibrated dosing algorithms in Colombia. The analytic framework and variant catalogue generated knowledge to operationalize precision pharmacotherapy across admixed Latin-American populations.</jats:p></jats:sec>","journal":"Frontiers in Pharmacology","year":2025,"id":633070,"datarank":0.16479184330021646,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.0,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1641191,"name":"Kevin Fernando Montoya-Quintero","orcid":null,"position":1,"is_corresponding":false},{"id":1641193,"name":"Johana Galván-Barrios","orcid":null,"position":2,"is_corresponding":false},{"id":1641195,"name":"Indiana Luz Rojas Torres","orcid":null,"position":3,"is_corresponding":false},{"id":1641190,"name":"Andy A. Acosta-Monterrosa","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Pharmacogenomics and genetic ancestry in Colombia: a study on all variant drug annotations of PharmGKB","abstract":"<jats:sec><jats:title>Background</jats:title><jats:p>To generate an ancestry-resolved pharmacogenomic (PGx) landscape for Colombia by integrating all PharmGKB variant-drug annotations with local allele-frequency data, thereby quantifying inter-ancestry differences of clinical relevance and exposing evidence gaps that hinder equitable precision medicine.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We conducted a cross-sectional analysis of 4,462 PharmGKB variant annotations (1994–2024), retaining 1,216 significant single-nucleotide polymorphisms (SNPs) reported in 552 studies. Allele frequencies were extracted for five Colombian populations: two predominantly African (Palenque [PLQ], Chocó [CHG]) and three predominantly European (ATQCES, ATQPGC, CLM), from the CÓDIGO database. Spearman correlations compared population-specific PGx profiles; SNPs with &amp;gt;25 percentage-point frequency differentials were tabulated.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>European ancestry dominated the global evidence base, representing 51.5% of 651,532 participants, while African ancestry accounted for only 0.46% (n = 3,031). Strong correlations were observed among European-leaning Antioquians (<jats:italic>r</jats:italic><jats:sup>2</jats:sup> ≥ 0.90), whereas PLQ exhibited inverse or negligible correlations with those groups (<jats:italic>r</jats:italic><jats:sup>2</jats:sup> = −0.20 to −0.02) and minimal similarity with CHG (<jats:italic>r</jats:italic><jats:sup>2</jats:sup> = 0.12). Twenty-eight SNPs were frequent in PLQ (&amp;gt;75%) but rare in Europeans (&amp;lt;50%), and 44 showed the opposite pattern. Notable examples include CYP3A4 rs3735451-C (rivaroxaban; 87.1% vs. 23.2%), CYP3A5 rs776746-T (tacrolimus; 85% vs. 23.5%), and rs55881666-C (duloxetine; 15% vs. 84%). Globally, 71.5% of PGx studies originated in high-income countries.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Large, clinically actionable allele-frequency contrasts and pronounced discovery biases confirm the need for ancestry-aware PGx testing and locally calibrated dosing algorithms in Colombia. The analytic framework and variant catalogue generated knowledge to operationalize precision pharmacotherapy across admixed Latin-American populations.</jats:p></jats:sec>","is_dataset_classified":null,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"40949159","pmcid":"PMC12425994","openalex_id":"https://openalex.org/W4413803759","authors":[],"funders":[],"total_grants":0,"fwci":1.8597,"citation_percentile":0.8510343,"influential_citations":0,"citation_trend":[{"year":2026,"count":2}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1636451/pdf","host_type":"journal"},{"url":"https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1636451/pdf","host_type":"publisher"},{"url":"https://www.frontiersin.org/articles/10.3389/fphar.2025.1636451/full","host_type":"publisher"},{"url":"https://doi.org/10.3389/fphar.2025.1636451","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/40949159","host_type":"repository"},{"url":"https://doaj.org/article/2ed1a895dcbd409bbc8d5319b08107f9","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12425994/","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC12425994","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC12425994?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Pharmacogenetics and Drug Metabolism","Genetic Associations and Epidemiology","Genomics and Rare Diseases"],"mesh_terms":[],"keywords":["Pharmacogenomics","Single-nucleotide polymorphism","Ancestry-informative marker","Allele frequency","Genetics","Allele","Population","Biology","Medicine","Genotype","Gene","Genomics","Colombia","Pharmacogenetics","Precision Medicine","Pharmacogenomic Variants"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T10:53:44.446904Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}