{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T14:17:37Z","timestamp":1788445057011,"version":"build-2803163510"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T00:00:00Z","timestamp":1779408000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012264","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012264","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"NHLBI","doi-asserted-by":"publisher","award":["R01HL170627"],"award-info":[{"award-number":["R01HL170627"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021671","name":"National Cancer Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100021671","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The Duffy null variant (CC genotype) is associated with lower absolute neutrophil count (ANC) and increased risk of early discontinuation or ineligibility for certain treatments. Our primary objective was to evaluate the change in ANC over time among individuals on azathioprine or methotrexate. We also evaluated normality status (i.e., a designation of abnormal vs not) of ANC under genotype-adjusted and unadjusted thresholds.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We used the UK Biobank to calculate genotype-adjusted and unadjusted thresholds. We included participants reporting azathioprine or methotrexate use in All of Us to examine the primary and secondary objectives. The primary outcome was the log-mean difference in ANC between 1 year before and 2 years post medication initiation. The secondary outcome was the odds of normality of ANC under genotype-adjusted vs unadjusted thresholds.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We found that in azathioprine users, those with the CC genotype had nonstatistically significant lower ANC (log-mean difference, \u22120.017; 95% CI, \u22120.072 to 0.038). For methotrexate, those with the CC genotype had a statistically significant lower ANC (log-mean difference, \u22120.042; 95% CI, \u22120.074 to \u22120.009). Evaluations of unadjusted ANC thresholds in those on azathioprine revealed that CC individuals were more likely to be abnormal (odds ratio [OR], 7.51; 95% CI, 1.64 to 34.43). Findings were similar for methotrexate (OR, 4.35; 95% CI, 1.48 to 12.79). However, under Duffy-adjusted thresholds, there were no significant differences between both genotypes in either treatment group: azathioprine (P = .491) and methotrexate (P = .269).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We conclude that Duffy-adjusted ANC reference ranges reduce the proportion of individuals classified as abnormal, with several implications for Duffy-null individuals.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jalm\/jfag056","type":"journal-article","created":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T11:33:58Z","timestamp":1776166438000},"page":"1039-1049","source":"Crossref","is-referenced-by-count":1,"title":["Clinical Implications of the Duffy-Null Genotype in Patients on Azathioprine or Methotrexate in the All of Us Cohort"],"prefix":"10.1093","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-7617-0677","authenticated-orcid":false,"given":"Edgar","family":"Asiimwe","sequence":"first","affiliation":[{"name":"National Clinician Scholars Program (NCSP), UCSF , SanFrancisco, CA ,","place":["United States"]},{"name":"Department of General Internal Medicine (DGIM), Mt. Zion at UCSF , SanFrancisco, CA ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0351-001X","authenticated-orcid":false,"given":"Donglei","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of General Internal Medicine (DGIM), Mt. Zion at UCSF , SanFrancisco, CA ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Cheng","sequence":"additional","affiliation":[{"name":"Division of Oral Epidemiology & Public Health, UCSF , SanFrancisco, CA ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan H B","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, UCSF , SanFrancisco, CA ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence H","family":"Kushi","sequence":"additional","affiliation":[{"name":"Division of Research, Kaiser Permanente Northern California , Oakland, CA ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5447-0436","authenticated-orcid":false,"given":"Franklin W","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, UCSF , SanFrancisco, CA ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Kachuri","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Population Health, Stanford University , Stanford, CA ,","place":["United States"]},{"name":"Stanford Cancer Institute, Stanford University School of Medicine , Stanford, CA ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akinyemi","family":"Oni-Orisan","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, UCSF , SanFrancisco, CA ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2324-2884","authenticated-orcid":false,"given":"Elad","family":"Ziv","sequence":"additional","affiliation":[{"name":"Department of General Internal Medicine (DGIM), Mt. Zion at UCSF , SanFrancisco, CA ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,5,22]]},"reference":[{"key":"2026090309521168800_jfag056-B1","doi-asserted-by":"crossref","first-page":"3341","DOI":"10.1093\/hmg\/ddaa208","article-title":"The Duffy-null genotype and risk of infection","volume":"29","author":"Legge","year":"2020","journal-title":"Hum Mol Genet"},{"key":"2026090309521168800_jfag056-B2","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1136\/jcp.37.2.188","article-title":"Normal values for peripheral blood white cell counts in women of four different ethnic origins","volume":"37","author":"Bain","year":"1984","journal-title":"J Clin Pathol"},{"key":"2026090309521168800_jfag056-B3","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1016\/S0140-6736(71)90335-7","article-title":"Genetic neutropenia in people of African origin","volume":"2","author":"Shaper","year":"1971","journal-title":"Lancet (London, England)"},{"key":"2026090309521168800_jfag056-B4","doi-asserted-by":"crossref","DOI":"10.1016\/j.blre.2019.06.003","article-title":"Benign ethnic neutropenia","volume":"37","author":"Atallah-Yunes","year":"2019","journal-title":"Blood Rev"},{"key":"2026090309521168800_jfag056-B5","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1038\/ng0695-224","article-title":"Disruption of a GATA motif in the Duffy gene promoter abolishes erythroid gene expression in Duffy-negative individuals","volume":"10","author":"Tournamille","year":"1995","journal-title":"Nat Genet"},{"key":"2026090309521168800_jfag056-B6","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1111\/bjh.15730","article-title":"The Duffy antigen receptor for chemokines, ACKR1,\u2014\u2018Jeanne DARC\u2019 of benign neutropenia","volume":"184","author":"Rappoport","year":"2019","journal-title":"Br J Haematol"},{"key":"2026090309521168800_jfag056-B7","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.ajhg.2007.09.003","article-title":"Admixture mapping of white cell count: genetic locus responsible for lower white blood cell count in the Health ABC and Jackson Heart studies","volume":"82","author":"Nalls","year":"2008","journal-title":"Am J Hum Genet"},{"key":"2026090309521168800_jfag056-B8","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1182\/bloodadvances.2022007679","article-title":"Absolute neutrophil count by Duffy status among healthy Black and African American adults","volume":"7","author":"Merz","year":"2023","journal-title":"Blood Adv"},{"key":"2026090309521168800_jfag056-B9","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1038\/ncomms1265","article-title":"The global distribution of the Duffy blood group","volume":"2","author":"Howes","year":"2011","journal-title":"Nat Commun"},{"key":"2026090309521168800_jfag056-B10","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1000360","article-title":"Reduced neutrophil count in people of African descent is due to a regulatory variant in the Duffy antigen receptor for chemokines gene","volume":"5","author":"Reich","year":"2009","journal-title":"PLoS Genet"},{"key":"2026090309521168800_jfag056-B11","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1002108","article-title":"Genome-wide association study of white blood cell count in 16,388 African Americans: the continental origins and genetic epidemiology network (COGENT)","volume":"7","author":"Reiner","year":"2011","journal-title":"PLoS Genet"},{"key":"2026090309521168800_jfag056-B12","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0194400","article-title":"Analyses of genome wide association data, cytokines, and gene expression in African-Americans with benign ethnic neutropenia","volume":"13","author":"Charles","year":"2018","journal-title":"PLoS One"},{"key":"2026090309521168800_jfag056-B13","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.transci.2011.07.006","article-title":"Blood group antigens frequencies in the northeast of Iran","volume":"45","author":"Keramati","year":"2011","journal-title":"Transfus Apher Sci"},{"key":"2026090309521168800_jfag056-B14","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1111\/j.1365-2141.2008.07335.x","article-title":"Duffy (Fy), DARC, and neutropenia among women from the United States, Europe and the Caribbean","volume":"143","author":"Grann","year":"2008","journal-title":"Br J Haematol"},{"key":"2026090309521168800_jfag056-B15","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1182\/blood.2020008600","article-title":"When non-Whiteness becomes a condition","volume":"137","author":"Merz","year":"2021","journal-title":"Blood"},{"key":"2026090309521168800_jfag056-B16","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.7326\/M21-4675","article-title":"Race, genotype, and azathioprine discontinuation\u202f: a cohort study","volume":"175","author":"Dickson","year":"2022","journal-title":"Ann Intern Med"},{"key":"2026090309521168800_jfag056-B17","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1200\/JGO.2016.008318","article-title":"PALOMA-3: phase III trial of fulvestrant with or without palbociclib in premenopausal and postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer that progressed on prior endocrine therapy-safety and efficacy in Asian patients","volume":"3","author":"Iwata","year":"2017","journal-title":"J Glob Oncol"},{"key":"2026090309521168800_jfag056-B18","doi-asserted-by":"crossref","first-page":"1969","DOI":"10.1056\/NEJMp2409329","article-title":"The Duffy null phenotype\u2014addressing a source of discrimination in cancer care","volume":"391","author":"Hantel","year":"2024","journal-title":"N Engl J Med"},{"key":"2026090309521168800_jfag056-B19","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1182\/blood.2025029359","article-title":"Multinational assessment of absolute neutrophil counts and white blood cell counts among healthy Duffy null adults","volume":"147","author":"Hibbs","year":"2026","journal-title":"Blood"},{"key":"2026090309521168800_jfag056-B20","author":"All of Us Research Program | NIH"},{"key":"2026090309521168800_jfag056-B21","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1038\/s41586-023-06957-x","article-title":"Genomic data in the All of Us Research Program","volume":"627","author":"All of Us Research Program Genomics Investigators","year":"2024","journal-title":"Nature"},{"key":"2026090309521168800_jfag056-B22","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1038\/s41586-018-0579-z","article-title":"The UK Biobank resource with deep phenotyping and genomic data","volume":"562","author":"Bycroft","year":"2018","journal-title":"Nature"},{"key":"2026090309521168800_jfag056-B23","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1016\/j.ajhg.2021.08.004","article-title":"Genetic determinants of blood-cell traits influence susceptibility to childhood acute lymphoblastic leukemia","volume":"108","author":"Kachuri","year":"2021","journal-title":"Am J Hum Genet"},{"key":"2026090309521168800_jfag056-B24","doi-asserted-by":"crossref","DOI":"10.1001\/jamanetworkopen.2024.32475","article-title":"Cancer trial eligibility and therapy modifications for individuals with Duffy null-associated neutrophil count","volume":"7","author":"Hibbs","year":"2024","journal-title":"JAMA Netw Open"},{"key":"2026090309521168800_jfag056-B25","doi-asserted-by":"crossref","DOI":"10.1002\/hem3.70236","article-title":"Medical haematology trial eligibility and the Duffy null-associated neutrophil count: a cross-sectional study","volume":"9","author":"Tsiamita","year":"2025","journal-title":"HemaSphere"},{"key":"2026090309521168800_jfag056-B26","doi-asserted-by":"crossref","first-page":"3622","DOI":"10.1002\/cncr.33620","article-title":"Hematologic safety of palbociclib in combination with endocrine therapy in patients with benign ethnic neutropenia and advanced breast cancer","volume":"127","author":"Lynce","year":"2021","journal-title":"Cancer"},{"key":"2026090309521168800_jfag056-B27","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.schres.2023.08.002","article-title":"Clozapine and neutrophil response in patients of African descent: a six-month, multinational, prospective, open-label clinical trial","volume":"268","author":"Kelly","year":"2024","journal-title":"Schizophr Res"},{"key":"2026090309521168800_jfag056-B28","doi-asserted-by":"crossref","first-page":"2088","DOI":"10.1001\/jama.2023.7467","article-title":"Development of Duffy null-specific absolute neutrophil count reference ranges","volume":"329","author":"Merz","year":"2023","journal-title":"JAMA"},{"key":"2026090309521168800_jfag056-B29","doi-asserted-by":"crossref","first-page":"1633","DOI":"10.1200\/JCO.2009.24.3881","article-title":"Neutrophil count in African Americans: lowering the target cutoff to initiate or resume chemotherapy?","volume":"28","author":"Hsieh","year":"2010","journal-title":"J Clin Oncol"},{"key":"2026090309521168800_jfag056-B30","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1001\/jamaoncol.2017.4658","article-title":"Laboratory eligibility criteria as potential barriers to participation by black men in prostate cancer clinical trials","volume":"4","author":"Vastola","year":"2018","journal-title":"JAMA Oncol"},{"key":"2026090309521168800_jfag056-B31","doi-asserted-by":"crossref","first-page":"e909","DOI":"10.4088\/JCP.15r10085","article-title":"Benign ethnic neutropenia and clozapine use: a systematic review of the evidence and treatment recommendations","volume":"77","author":"Manu","year":"2016","journal-title":"J Clin Psychiatry"},{"key":"2026090309521168800_jfag056-B32","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1093\/jamia\/ocae293","article-title":"Clinical implementation of preemptive pharmacogenomics testing for personalized medicine at an academic medical center","volume":"32","author":"Tamraz","year":"2025","journal-title":"J Am Med Inform Assoc"},{"key":"2026090309521168800_jfag056-B33","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1002\/cpt.3736","article-title":"Progress in pharmacogenomics implementation in the United States: barrier erosion and remaining challenges","volume":"118","author":"Smith","year":"2025","journal-title":"Clin Pharmacol Ther"},{"key":"2026090309521168800_jfag056-B34","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1111\/vox.12273","article-title":"Duffy blood group phenotype-genotype correlations using high-resolution melting analysis PCR and microarray reveal complex cases including a new null FY*A allele: the role for sequencing in genotyping algorithms","volume":"109","author":"Lopez","year":"2015","journal-title":"Vox Sang"},{"key":"2026090309521168800_jfag056-B35","doi-asserted-by":"crossref","first-page":"2202","DOI":"10.1038\/ajg.2010.202","article-title":"Racial disparities in utilization of specialist care and medications in inflammatory bowel disease","volume":"105","author":"Nguyen","year":"2010","journal-title":"Am J Gastroenterol"},{"key":"2026090309521168800_jfag056-B36","doi-asserted-by":"crossref","first-page":"1452","DOI":"10.1182\/bloodadvances.2024014399","article-title":"Characterization of the phenotypic consequences of the Duffy-null genotype","volume":"9","author":"Hysong","year":"2025","journal-title":"Blood Adv"},{"key":"2026090309521168800_jfag056-B37","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1097\/MOH.0000000000000834","article-title":"Novel neutrophil biology insights underlying atypical chemokine receptor-1\/Duffy antigen receptor of chemokines-associated neutropenia","volume":"31","author":"Liu","year":"2024","journal-title":"Curr Opin Hematol"},{"key":"2026090309521168800_jfag056-B38","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1038\/ni.3763","article-title":"Atypical chemokine receptor 1 on nucleated erythroid cells regulates hematopoiesis","volume":"18","author":"Duchene","year":"2017","journal-title":"Nat Immunol"},{"key":"2026090309521168800_jfag056-B39","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1016\/j.cell.2020.06.045","article-title":"Trans-ethnic and ancestry-specific blood-cell genetics in 746,667 individuals from 5 global populations","volume":"182","author":"Chen","year":"2020","journal-title":"Cell"},{"key":"2026090309521168800_jfag056-B40","doi-asserted-by":"crossref","first-page":"1836","DOI":"10.1016\/j.ajhg.2021.08.007","article-title":"Whole-genome sequencing in diverse subjects identifies genetic correlates of leukocyte traits: the NHLBI TOPMed program","volume":"108","author":"Mikhaylova","year":"2021","journal-title":"Am J Hum Genet"}],"container-title":["The Journal of Applied Laboratory Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jalm\/article-pdf\/11\/5\/1039\/68364644\/jfag056.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jalm\/article-pdf\/11\/5\/1039\/68364644\/jfag056.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T13:52:35Z","timestamp":1788443555000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jalm\/article\/11\/5\/1039\/8690297"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,22]]},"references-count":40,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5,22]]},"published-print":{"date-parts":[[2026,9,3]]}},"URL":"https:\/\/doi.org\/10.1093\/jalm\/jfag056","relation":{},"ISSN":["2475-7241"],"issn-type":[{"value":"2475-7241","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,9]]},"published":{"date-parts":[[2026,5,22]]}}}