{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T16:23:20Z","timestamp":1791476600091,"version":"4.3.4"},"reference-count":11,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,4,27]],"date-time":"2025-04-27T00:00:00Z","timestamp":1745712000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:p>Concerns about the applicability of pharmacogenetic (PGx) testing across diverse ancestry groups have risen from the underrepresentation of non\u2010European populations in PGx research. Current PGx panels may fail to detect relevant variants in non\u2010European populations, increasing the likelihood of false\u2010negative results. To investigate this, we assessed reference allele (*1) and genotype (*1\/*1) frequencies by self\u2010reported ancestry in a cohort of 1086 youth aged 6\u201324\u2009years who underwent PGx testing. Testing included 10 pharmacogenes (<jats:italic>CYP2B6<\/jats:italic>, <jats:italic>CYP2C19<\/jats:italic>, <jats:italic>CYP2C9<\/jats:italic>, <jats:italic>CYP2D6<\/jats:italic>, <jats:italic>CYP3A4<\/jats:italic>, <jats:italic>CYP3A5<\/jats:italic>, <jats:italic>NUDT15<\/jats:italic>, <jats:italic>SLCO1B1<\/jats:italic>, <jats:italic>TPMT<\/jats:italic>, and <jats:italic>VKORC1<\/jats:italic>) using a panel covering all Association for Molecular Pathology Tier 1 alleles and 53% of Tier 2 alleles. Compared with Europeans (<jats:italic>n<\/jats:italic>\u2009=\u2009727), non\u2010Europeans (<jats:italic>n<\/jats:italic>\u2009=\u2009359) had higher *1 allele frequencies for <jats:italic>CYP2C9<\/jats:italic>, <jats:italic>CYP2D6<\/jats:italic>, and <jats:italic>CYP3A5<\/jats:italic> (all <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.01), while Europeans had higher frequencies for <jats:italic>CYP2C19<\/jats:italic> and <jats:italic>VKORC1<\/jats:italic> (all <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.01). Similarly, *1\/*1 genotype frequencies were higher in non\u2010Europeans for <jats:italic>CYP2C9<\/jats:italic> and <jats:italic>CYP3A4<\/jats:italic> (all <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.01), but higher in Europeans for <jats:italic>VKORC1<\/jats:italic> (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.01). False\u2010negative estimates exceeded 1% for <jats:italic>CYP2B6<\/jats:italic>, <jats:italic>CYP2D6<\/jats:italic>, <jats:italic>CYP2C9<\/jats:italic>, <jats:italic>CYP2C19<\/jats:italic>, and <jats:italic>SLCO1B1<\/jats:italic> in at least one ancestry group. These findings support the notion that *1 allele and *1\/*1 genotype frequencies are more frequent in non\u2010Europeans for specific genes, but Europeans are also at comparable risk for false\u2010negative results. Expanded allele coverage on PGx panels could mitigate false\u2010negative risks, improving equity in PGx testing across diverse populations.<\/jats:p>","DOI":"10.1002\/cpt.3697","type":"journal-article","created":{"date-parts":[[2025,4,27]],"date-time":"2025-04-27T12:33:12Z","timestamp":1745757192000},"page":"331-336","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Estimating the Frequency of False\u2010Negative Pharmacogenetic Test Results by Self\u2010Reported Ancestry"],"prefix":"10.1002","volume":"118","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-5325-8897","authenticated-orcid":false,"given":"Weng\u2010Sam","family":"Siu","sequence":"first","affiliation":[{"name":"Cumming School of Medicine University of Calgary  Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7438-4551","authenticated-orcid":false,"given":"Abdullah Al","family":"Maruf","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Rady Faculty of Health Sciences University of Manitoba  Winnipeg Manitoba Canada"},{"name":"Children's Hospital Research Institute of Manitoba  Winnipeg Manitoba Canada"},{"name":"The Mathison Centre for Mental Health Research &amp; Education Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary  Calgary Alberta Canada"},{"name":"Department of Psychiatry University of Calgary  Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8551-4530","authenticated-orcid":false,"given":"Sarker M.","family":"Shaheen","sequence":"additional","affiliation":[{"name":"The Mathison Centre for Mental Health Research &amp; Education Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary  Calgary Alberta Canada"},{"name":"Department of Psychiatry University of Calgary  Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryden","family":"McCloud","sequence":"additional","affiliation":[{"name":"The Mathison Centre for Mental Health Research &amp; Education Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary  Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6268-8495","authenticated-orcid":false,"given":"Madison","family":"Heintz","sequence":"additional","affiliation":[{"name":"The Mathison Centre for Mental Health Research &amp; Education Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary  Calgary Alberta Canada"},{"name":"Department of Medical Genetics University of Calgary  Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3663-5019","authenticated-orcid":false,"given":"Laina","family":"McAusland","sequence":"additional","affiliation":[{"name":"The Mathison Centre for Mental Health Research &amp; Education Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary  Calgary Alberta Canada"},{"name":"Department of Psychiatry University of Calgary  Calgary Alberta Canada"},{"name":"Department of Medical Genetics University of Calgary  Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2496-4624","authenticated-orcid":false,"given":"Paul D.","family":"Arnold","sequence":"additional","affiliation":[{"name":"The Mathison Centre for Mental Health Research &amp; Education Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary  Calgary Alberta Canada"},{"name":"Department of Psychiatry University of Calgary  Calgary Alberta Canada"},{"name":"Department of Medical Genetics University of Calgary  Calgary Alberta Canada"},{"name":"Alberta Children's Hospital Research Institute University of Calgary  Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6303-8696","authenticated-orcid":false,"given":"Chad A.","family":"Bousman","sequence":"additional","affiliation":[{"name":"The Mathison Centre for Mental Health Research &amp; Education Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary  Calgary Alberta Canada"},{"name":"Department of Psychiatry University of Calgary  Calgary Alberta Canada"},{"name":"Department of Medical Genetics University of Calgary  Calgary Alberta Canada"},{"name":"Alberta Children's Hospital Research Institute University of Calgary  Calgary Alberta Canada"},{"name":"Department of Physiology &amp; Pharmacology University of Calgary  Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,4,27]]},"reference":[{"key":"e_1_2_10_1_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1432"},{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmoldx.2021.11.008"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2021.719671"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes14101945"},{"key":"e_1_2_10_5_1","article-title":"Approaches and hurdles of implementing pharmacogenetic testing in the psychiatric clinic","volume":"1","author":"Maruf A.A.","year":"2022","journal-title":"PCN Rep. Psychiatr. Clin. Neurosci."},{"key":"e_1_2_10_6_1","first-page":"130","article-title":"Pharmacogenomic allele coverage of genome\u2010wide genotyping arrays: a comparative analysis","volume":"34","author":"Lenz C.","year":"2024","journal-title":"Pharmacogenet. Genomics"},{"key":"e_1_2_10_7_1","unstructured":"PharmGKB [Internet].AMP's Minimum Sets of Alleles for PGx Testing<https:\/\/www.pharmgkb.org\/ampAllelesToTest>."},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1322"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2350"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1080\/17512433.2024.2307418"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/jalm\/jfad097"}],"container-title":["Clinical Pharmacology &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.3697","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T08:52:21Z","timestamp":1752828741000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1002\/cpt.3697"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,27]]},"references-count":11,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,8]]}},"alternative-id":["10.1002\/cpt.3697"],"URL":"https:\/\/doi.org\/10.1002\/cpt.3697","archive":["Portico"],"relation":{},"ISSN":["0009-9236","1532-6535"],"issn-type":[{"value":"0009-9236","type":"print"},{"value":"1532-6535","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,27]]},"assertion":[{"value":"2025-02-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}