{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T19:24:08Z","timestamp":1785785048143,"version":"3.56.0"},"reference-count":19,"publisher":"American Society of Hematology","issue":"26","license":[{"start":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T00:00:00Z","timestamp":1759190400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,12,25]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>To identify genetic variants that influence myeloproliferative neoplasm (MPN) phenotypes, we undertook a 2-stage patient-only genome-wide association study. MPN subtypes (essential thrombocythemia [ET]; polycythemia vera [PV]) were compared with each other to healthy controls and stratified analyses was performed for chromosome 9p aberrations, JAK2 V617F mutation burden, and sex. The ET vs PV analysis identified known associations: (1) at HBS1L-MYB that increased ET risk (Pmeta = 7.93 \u00d7 10\u20136, odds ratio [OR] = 1.28) and reduced PV risk (Pmeta = 9.43 \u00d7 10\u20135, OR = 0.81) and (2) at GFI1B-GTF3C5 that predisposed to PV only (Pmeta = 1.43 \u00d7 10\u20139, OR = 1.38). Two further linked intronic variants, rs2425786 and rs2425788, at CDH22\/CD40 were significant in females only (Pmeta = 2.67 \u00d7 10\u20138), with predisposition to PV (Pmeta = .0006, OR = 1.3) and reduction of ET risk (Pmeta = 7.82 \u00d7 10\u20135, OR = 0.75). A polygenic risk score consisting of 48 variants from 31 loci demonstrated moderate discriminative performance for ET and PV (area under the curve [AUC] = 0.718) and was improved by optimization for disease subtype (AUCET = 0.724 and AUCPV = 0.755). Overall, our results reveal that multiple germline variants influence MPN phenotype, with HBS1L-MYB and a novel sex-specific association with CDH22\/CD40 being the strongest determinants.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1182\/blood.2025028489","type":"journal-article","created":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T19:04:12Z","timestamp":1759259052000},"page":"3228-3233","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":4,"title":["Genome-wide analysis defines genetic determinants of MPN subtypes and identifies a sex-specific association at\n                    <i>CDH22<\/i>\n                    \/\n                    <i>CD40<\/i>"],"prefix":"10.1182","volume":"146","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5896-1889","authenticated-orcid":false,"given":"William J.","family":"Tapper","sequence":"first","affiliation":[{"name":"1Faculty of Medicine, University of Southampton, Southampton, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0164-7773","authenticated-orcid":false,"given":"Ahmed A. 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Joanna","family":"Baxter","sequence":"additional","affiliation":[{"name":"2Department of Haematology, University of Cambridge, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne","family":"Ewing","sequence":"additional","affiliation":[{"name":"3Department of Haematology, Heartlands Hospital, Birmingham, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"Wallis","sequence":"additional","affiliation":[{"name":"4Department of Haematology, Royal Bournemouth Hospital, Bournemouth, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1809-284X","authenticated-orcid":false,"given":"Paola","family":"Guglielmelli","sequence":"additional","affiliation":[{"name":"5Center Research and Innovation of Myeloproliferative Neoplasms, Dipartimento di Medicina Sperimentale e Clinica, Azienda Ospedaliero Universitaria Careggi, University of Florence, Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dolors","family":"Colomer","sequence":"additional","affiliation":[{"name":"6Hospital Clinic, Institut Investigacions Biom\u00e8diques August Pi i Sunyer, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer, Universitat Barcelona, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5335-2726","authenticated-orcid":false,"given":"Beatriz","family":"Bellosillo","sequence":"additional","affiliation":[{"name":"7Hospital del Mar, Hospital del Mar Research Institute, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Montse","family":"Gomez","sequence":"additional","affiliation":[{"name":"8Hospital Cl\u00ednico Universitario, Instituto de Investigaci\u00f3n Sanitaria, University of Valencia, Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4289-3113","authenticated-orcid":false,"given":"Juan Carlos","family":"Hern\u00e1ndez-Boluda","sequence":"additional","affiliation":[{"name":"8Hospital Cl\u00ednico Universitario, Instituto de Investigaci\u00f3n Sanitaria, University of Valencia, Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Besses","sequence":"additional","affiliation":[{"name":"7Hospital del Mar, Hospital del Mar Research Institute, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Cervantes","sequence":"additional","affiliation":[{"name":"6Hospital Clinic, Institut Investigacions Biom\u00e8diques August Pi i Sunyer, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer, Universitat Barcelona, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1011-8171","authenticated-orcid":false,"given":"Steffen","family":"Koschmieder","sequence":"additional","affiliation":[{"name":"9Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Faculty of Medicine, RWTH Aachen University, Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony R.","family":"Green","sequence":"additional","affiliation":[{"name":"2Department of Haematology, University of Cambridge, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Reiter","sequence":"additional","affiliation":[{"name":"10University Hospital Mannheim, Heidelberg University, Mannheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5755-0730","authenticated-orcid":false,"given":"Alessandro","family":"Vannucchi","sequence":"additional","affiliation":[{"name":"5Center Research and Innovation of Myeloproliferative Neoplasms, Dipartimento di Medicina Sperimentale e Clinica, Azienda Ospedaliero Universitaria Careggi, University of Florence, Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Harrison","sequence":"additional","affiliation":[{"name":"11Department of Haematology, Guy\u2019s and St Thomas\u2019 National Health Service Foundation Trust, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5481-2555","authenticated-orcid":false,"given":"Nicholas C. 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