{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T22:03:42Z","timestamp":1789423422143,"version":"build-2803163510"},"reference-count":53,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:p>\n                    Genetic variation contributes substantially to interindividual and interpopulation differences in drug response, yet most pharmacogenomic studies remain biased toward European populations. Here, we systematically assessed pharmacogenomic variation across East Asians (EAS) and Europeans (EUR) using public genomic datasets and investigated the potential evolutionary forces shaping these differences. Our analyses revealed that EAS populations generally harbor a lower frequency of pharmacogenomic variants previously associated with reduced drug response compared with EUR populations, indicating population\u2010level differences in the distribution of PGx variants. Drug\u2010associated genes exhibited threefold higher population differentiation than the genome\u2010wide background (\n                    <jats:italic>F<\/jats:italic>\n                    <jats:sub>ST<\/jats:sub>\n                    \u2009=\u20090.18 vs. 0.06). Key transport genes such as\n                    <jats:italic>SLCO1B3\/SLCO1B7<\/jats:italic>\n                    showed striking differences in cumulative allele probability (EAS: 18.69% vs. EUR: 91.60%), suggesting population\u2010level divergence in drug transport and pharmacokinetics. Population genetic analyses revealed stronger signals of positive selection on PGx variants in EAS populations, likely reflecting historical adaptations to pathogen and dietary pressures. For instance, the\n                    <jats:italic>VKORC1<\/jats:italic>\n                    \u2010rs9923231\u2010T allele, which enhances warfarin sensitivity, shows evidence of selection in EAS populations (XP\u2010EHH\u2009=\u20093.58) and may relate to vitamin K intake. Conversely, the EUR\u2010enriched\n                    <jats:italic>SH2B3<\/jats:italic>\n                    \u2010rs3184504\u2010T allele (AF\n                    <jats:sub>EUR<\/jats:sub>\n                    : 0.46 vs. AF\n                    <jats:sub>EAS<\/jats:sub>\n                    : 0.003) has been associated with selection related to blood pressure regulation. Collectively, these findings highlight the importance of incorporating population diversity into pharmacogenomic research and underscore the potential need for population\u2010specific drug response guidelines to advance global precision medicine.\n                  <\/jats:p>","DOI":"10.1002\/cpt.70354","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T12:15:01Z","timestamp":1780488901000},"page":"510-519","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Population Genomics Insights into Pharmacogenomic Differentiation Between East Asians and Europeans"],"prefix":"10.1002","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2287-1133","authenticated-orcid":false,"given":"Sihan","family":"Chen","sequence":"first","affiliation":[{"name":"State Key Laboratory of Genetics and Development of Complex Phenotypes, Center for Evolutionary Biology, School of Life Sciences Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9667-1141","authenticated-orcid":false,"given":"Hongpu","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Genetics and Development of Complex Phenotypes, Center for Evolutionary Biology, School of Life Sciences Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1975-1002","authenticated-orcid":false,"given":"Shuhua","family":"Xu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Genetics and Development of Complex Phenotypes, Center for Evolutionary Biology, School of Life Sciences Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,3]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.0306-5251.2001.01498.x"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)31276-0"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-022-00572-8"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/tpj.2016.77"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-021-01681-6"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.12771"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.163.1.28"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12266"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01672-4"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2021.11.008"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2520"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1720"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature15393"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aay5012"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41597-024-03031-7"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature15394"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/nsr\/nwad077"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-12-323"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2350"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-016-0974-4"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1558-5646.1984.tb05657.x"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btr330"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkg509"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth0410-248"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-017-0502-5"},{"key":"e_1_2_9_26_1","first-page":"701","article-title":"Nonparametric inference for a family of counting processes","volume":"6","author":"Odd A.","year":"1978","journal-title":"Annals Stat."},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0040072"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature06250"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/msu211"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-294X.2005.02683.x"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/msy006"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-08588-0"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.118.114934"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2020.105155"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1074"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/tpj.2016.1"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13760-020-01454-8"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/tpj.2011.45"},{"key":"e_1_2_9_39_1","article-title":"The global epidemiology of Kawasaki disease: review and future perspectives","volume":"2017","author":"Lin M.T.","year":"2017","journal-title":"Glob Cardiol Sci Pract"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/jvh.12467"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiq154"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGENETICS.112.964080"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1097\/MNH.0000000000000196"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.121.320625"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbspin.2012.02.003"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00335-021-09926-9"},{"key":"e_1_2_9_47_1","first-page":"1236","article-title":"Global gene expression profiling of pancreatic islets in mice during streptozotocin\u2010induced \u03b2\u2010cell damage and pancreatic Glp\u20101 gene therapy","volume":"6","author":"Tonne J.M.","year":"2013","journal-title":"Dis. Model. Mech."},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.tpj.6500313"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.2217\/pgs-2018-0189"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-018-2483-8"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/phar.1982"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0053049"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2025.09.004"}],"container-title":["Clinical Pharmacology &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.70354","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cpt.70354","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.70354","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T03:18:47Z","timestamp":1783912727000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1002\/cpt.70354"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,3]]},"references-count":53,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1002\/cpt.70354"],"URL":"https:\/\/doi.org\/10.1002\/cpt.70354","archive":["Portico"],"relation":{},"ISSN":["0009-9236","1532-6535"],"issn-type":[{"value":"0009-9236","type":"print"},{"value":"1532-6535","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,3]]},"assertion":[{"value":"2025-12-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-20","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}