{ "abstract": "Clozapine is licenced for treatment‐resistant schizophrenia and psychosis in Parkinson's disease. In the United Kingdom, there is a mandatory requirement for absolute neutrophil count (ANC) and white blood cell count (WBC) monitoring to safeguard against agranulocytosis. Some people have naturally low ANCs without increased infection risk, caused by a homozygous T > C variant in ACKR1 , commonly called the Duffy‐null genotype. This condition is known as ADAN ( ACKR1 / DARC ‐associated neutropenia) and synonyms include DANC (Duffy‐null associated neutrophil count) and BEN (benign ethnic neutropenia). It is usual UK practice to lower WBC/ANC thresholds for people confirmed to have ADAN. However, ADAN often remains undetected, resulting in unnecessary discontinuation and exclusion from clozapine. This CERSI‐PGx guideline provides a framework to offer ACKR1 genotype testing within the existing clinical pathway. We recommend three eligibility criteria, including pre‐emptive testing for all people starting clozapine, testing for people registered in the Central Non‐Rechallenge Database and reactive testing following a below‐threshold blood result (defined as ‘amber’ or ‘red’). We recommend that people with the Duffy‐null genotype should be monitored using revised WBC/ANC thresholds for ADAN. Regardless of ACKR1 genotype, haematology input is required for people returning a WBC < 2.0 × 10 9 /L and/or ANC < 1.0 × 10 9 /L who present with a key clinical feature, such as sustained temperature ≥38°C. Finally, we summarize health economic evidence, estimating in the first year of testing, 129 people with the Duffy‐null genotype could be identified, resulting in savings ranging from £42 732 to £727 990. We propose ACKR1 testing as a cost‐effective approach for facilitating access to clozapine, the optimal therapy for treatment‐resistant schizophrenia.", "abstract_shown": true, "affiliations": [ "Division of Psychiatry University College London London UK", "Belfast Health and Social Care Trust Belfast UK", "Genomics Unit National Health Service England London UK", "North Thames Genomic Medicine Service Alliance London UK", "The Side‐By‐Side Network London UK", "High Secure Intellectual Disability Service for Scotland and Northern Ireland Carstairs UK", "The Royal College of Psychiatrists London UK", "Institute of Pharmaceutical Science King's College London London UK", "Pharmacy Department South London and Maudsley NHS Foundation Trust London UK", "South East Genomic Medicine Service Alliance London UK", "Cardiff and Vale University Health Board Cardiff UK", "Department of Haematology King's College Hospital NHS Foundation Trust London UK", "Centre for Health Economics and Medicines Evaluation, North Wales Medical School Bangor University Bangor UK", "King's Health Economics, Institute of Psychiatry, Psychology and Neuroscience King's College London London UK", "Birmingham Women's and Children's NHS Foundation Trust Birmingham UK", "Research Department of Epilepsy, Queen Square Institute of Neurology University College London London UK", "Specialist Community Forensic Team for People With Learning Disability and Autism Hollins Park Hospital Warrington UK", "North West Genomic Laboratory Hub Manchester University NHS Foundation Trust Manchester UK", "NHS Blood and Transplant Bristol UK", "Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences Cardiff University Cardiff UK", "All Wales Medical Genomics Service Cardiff UK", "Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology University of Liverpool Liverpool UK", "Department of Translational Medicine and Surgery, Section of Pharmacology Università Cattolica del Sacro Cuore – Fondazione Policlinico Universitario A. Gemelli, IRCCS Rome Italy", "The Wolfson Centre for Personalised Medicine, Centre for Drug Safety Science University of Liverpool Liverpool UK", "North London NHS Foundation Trust London UK" ], "article_type": null, "arxiv": null, "author_total": 30, "authors": [ { "affs": [ 0 ], "name": "Stephen Murtough", "orcid": "0000-0002-7440-7095" }, { "affs": [ 0 ], "name": "Oriella Stellakis" }, { "affs": [ 0 ], "name": "Daisy Mills" }, { "affs": [ 1 ], "name": "Blanca Bjourson" }, { "affs": [ 2 ], "name": "Vicky Chaplin" }, { "affs": [ 3 ], "name": "Dharmisha Chauhan", "orcid": "0009-0002-1781-4011" }, { "affs": [ 4 ], "name": "Beverley Chipp", "orcid": "0000-0002-2890-8542" }, { "affs": [ 0 ], "name": "Marius Cotic", "orcid": "0000-0002-1481-9100" }, { "affs": [ 5, 6 ], "name": "Jana de Villiers", "orcid": "0009-0005-8658-7061" }, { "affs": [ 7, 8 ], "name": "Olubanké Dzahini", "orcid": "0000-0003-3878-2143" }, { "affs": [ 9 ], "name": "Frances Elmslie", "orcid": "0000-0002-2508-9107" }, { "affs": [ 10 ], "name": "Katie Evans", "orcid": "0009-0006-7581-692X" }, { "affs": [ 11 ], "name": "Shreyans Gandhi", "orcid": "0000-0003-3532-231X" }, { "affs": [ 12 ], "name": "D. O. HUGHES", "orcid": "0000-0001-8247-7459" }, { "affs": [ 13 ], "name": "Huajie Jin" }, { "affs": [ 0 ], "name": "Daniele Panconesi", "orcid": "0009-0001-1128-6687" }, { "affs": [ 14 ], "name": "Anna Skowrońska", "orcid": "0000-0003-3418-8198" }, { "affs": [ 15 ], "name": "Sanjay M. Sisodiya", "orcid": "0000-0002-1511-5893" }, { "affs": [ 16 ], "name": "Ed Silva" }, { "affs": [ 17 ], "name": "Vicky Stinton" }, { "affs": [ 11 ], "name": "Sara Stuart‐Smith" }, { "affs": [ 18 ], "name": "Sarah Tarrant" }, { "affs": [ 7, 8 ], "name": "David M. Taylor", "orcid": "0000-0002-2557-1710" }, { "affs": [ 0 ], "name": "Lauren Varney", "orcid": "0009-0009-1139-4790" }, { "affs": [ 19 ], "name": "James TR Walters", "orcid": "0000-0002-6980-4053" }, { "affs": [ 20, 10 ], "name": "Michelle Wood" }, { "affs": [ 14 ], "name": "Jessica Woodley", "orcid": "0009-0006-3076-6471" }, { "affs": [ 21, 22 ], "name": "Cinzia Dello Russo", "orcid": "0000-0002-2538-3832" }, { "affs": [ 21, 23 ], "name": "Munir Pirmohamed", "orcid": "0000-0002-7534-7266" }, { "affs": [ 0, 24 ], "name": "Elvira Bramon", "orcid": "0000-0003-1369-5983" } ], "bibtex": "https://research.draconitic.com/paper/fngbcj2mk2mmr.bib", "cited_by": 5, "doi": "10.1002/bcp.70576", "fulltext_url": null, "id": "fngbcj2mk2mmr", "issns": [ "0306-5251", "1365-2125" ], "landing_url": "https://doi.org/10.1002/bcp.70576", "language": "en", "licence": "CC-BY", "licence_label": "CC BY", "licence_source": "journal", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "openalex", "3004|Pharmacogenetics and Drug Metabolism" ] ], "openalex": "W7161022471", "pdf_url": null, "pmcid": "PMC13304278", "pmid": "42125771", "published": "2026-05-13", "publisher": "Wiley", "ris": "https://research.draconitic.com/paper/fngbcj2mk2mmr.ris", "sources": [ { "first_seen": "2026-10-30T13:26:56Z", "native_id": "W7161022471", "source": "openalex", "url": "https://doi.org/10.1002/bcp.70576" } ], "subjects": [ { "field": "medicine", "origin": "openalex:3004|Pharmacogenetics and Drug Metabolism", "subfield": "pharmacology-toxicology" } ], "title": "ACKR1 /Duffy‐null genotype testing for clozapine: A guideline developed by the UK Centre of Excellence in Regulatory Science and Innovation in Pharmacogenomics (CERSI‐PGx)", "title_text": "ACKR1 /Duffy‐null genotype testing for clozapine: A guideline developed by the UK Centre of Excellence in Regulatory Science and Innovation in Pharmacogenomics (CERSI‐PGx)", "type": "peer-reviewed", "updated_at": "2026-11-05T13:21:08Z", "url": "https://research.draconitic.com/paper/fngbcj2mk2mmr", "venue": "British Journal of Clinical Pharmacology", "versions": [] }