{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T02:33:34Z","timestamp":1787970814578,"version":"build-2784847793"},"reference-count":53,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,4,11]],"date-time":"2023-04-11T00:00:00Z","timestamp":1681171200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:p>Over 20% of US Food and Drug Administration (FDA)\u2010approved drugs in the United States are metabolized by the hepatic enzyme cytochrome P450 2D6 (CYP2D6). The gene encoding CYP2D6 is highly polymorphic and genetic variation has been shown to impact drug response for many commonly dispensed drugs including opioids and antidepressants. Thus, it is important to understand an individual's CYP2D6 metabolizer status to optimize treatment outcomes for patients taking medications that are metabolized by this enzyme. Consequently, clinical <jats:italic>CYP2D6<\/jats:italic> pharmacogenetic testing is being implemented by a growing number of health centers. Furthermore, clinical guidelines currently recommend adapting therapeutic regimens based on <jats:italic>CYP2D6<\/jats:italic> genotype\u2010informed phenotype. However, <jats:italic>CYP2D6<\/jats:italic> genetic variation varies considerably across global populations and many allelic variants, or star alleles, are predominantly found in certain ancestral populations. Although <jats:italic>CYP2D6<\/jats:italic> genetic variation has been extensively studied, there is still a paucity of information for many non\u2010European populations. As has been shown for other pharmacogenes in randomized controlled trials, results from European populations cannot simply be extrapolated to other groups and, in some cases, even has the potential to cause harm. Therefore, enhanced inclusion in pharmacogenetic studies is urgently needed to increase ancestral representation, determine the extent of global <jats:italic>CYP2D6<\/jats:italic> genetic variation (e.g., ancestry\u2010specific variants), and determine the clinical impact of this variation on clinical treatment outcome. This review highlights knowledge gaps, challenges, and future directions in <jats:italic>CYP2D6<\/jats:italic> pharmacogenomics through a unique pharmacoequity lens to address health inequities that hamper our ability to optimize drug therapy for improved pharmacological outcomes in diverse populations globally.<\/jats:p>","DOI":"10.1002\/cpt.2890","type":"journal-article","created":{"date-parts":[[2023,3,16]],"date-time":"2023-03-16T09:15:31Z","timestamp":1678958131000},"page":"69-76","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Advancing <scp><i>CYP2D6<\/i><\/scp> Pharmacogenetics through a Pharmacoequity Lens"],"prefix":"10.1111","volume":"114","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0392-4746","authenticated-orcid":false,"given":"Oyinlade","family":"Kehinde","sequence":"first","affiliation":[{"name":"Child and Adolescents Mental Health Service Center Federal Neuro\u2010Psychiatric Hospital  Lagos Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6417-3961","authenticated-orcid":false,"given":"Laura B.","family":"Ramsey","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Cincinnati College of Medicine  Cincinnati Ohio USA"},{"name":"Divisions of Clinical Pharmacology and Research in Patient Services Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6968-1893","authenticated-orcid":false,"given":"Andrea","family":"Gaedigk","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Toxicology &amp; Therapeutic Innovation Children's Mercy Research Institute (CMRI)  Kansas City Missouri USA"},{"name":"School of Medicine University of Missouri\u2010Kansas City  Kansas City Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5897-5543","authenticated-orcid":false,"given":"Akinyemi","family":"Oni\u2010Orisan","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy University of California San Francisco  San Francisco California USA"},{"name":"Institute for Human Genetics University of California San Francisco  San Francisco California USA"},{"name":"Department of Bioengineering and Therapeutic Sciences University of California San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,4,11]]},"reference":[{"key":"e_1_2_7_1_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-019-0484-3"},{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa041888"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0082562"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.2165\/11318070-000000000-00000"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcpt.13780"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2321"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.12692"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1643"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.clpt.6100406"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-022-03364-5"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm9092890"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.clpt.6100507"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2011.34"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431-021-01004-7"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431\u2010022\u201001262\u2010z"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431-021-00920-y"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1165"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmoldx.2021.05.013"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2149"},{"key":"e_1_2_7_20_1","first-page":"86","article-title":"FDA warns against use of codeine and tramadol in children and breastfeeding women","volume":"59","year":"2017","journal-title":"Med. 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