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The study identifies polygenic risk scores from monocyte count and plateletcrit as new risk factors for JAK2(V617F) positivity and shows trait-specific effects across different myeloproliferative neoplasm subtypes. Low risk scores for two platelet traits protect against essential thrombocythemia in carriers. Extreme hematological polygenic profiles may also support MPN diagnosis even without somatic driver mutations.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/inherited-polygenic-effects-on-common-hematological-traits-influence-clonal-selection-on-jak2v617f/330096/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/inherited-polygenic-effects-on-common-hematological-traits-influence-clonal-selection-on-jak2v617f/330096.png","ImageObject",300,407,{"name":92,"@type":93},"Himbo","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-03","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":44},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What does the study conclude about inherited polygenic effects and JAK2(V617F)?","Question",{"text":112,"@type":113},"Inherited polygenic loci that underlie common hematological traits influence the expansion of JAK2(V617F) clones and relate to downstream MPN phenotype development.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Which polygenic risk scores are identified as new risk factors for JAK2(V617F) positivity?",{"text":117,"@type":113},"Polygenic risk scores for monocyte count and plateletcrit are reported as new risk factors for JAK2(V617F) positivity.",{"name":119,"@type":110,"acceptedAnswer":120},"How do low polygenic risk scores affect essential thrombocythemia among JAK2(V617F) carriers?",{"text":121,"@type":113},"Low polygenic scores for two platelet traits show protective effects, making carriers two to three times less likely to have essential thrombocythemia than carriers with high polygenic scores.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},330096,1790141835,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":44,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":36,"preview_page_count":4},687197100911,"https://ap-avatar.wpscdn.com/avatar/a000239b6f1da00475?x-image-process=image/resize,m_fixed,w_180,h_180&k=1785132997149421697","| nature genetics |  |  | |\n| --- | --- | --- | --- |\n| Article [https://doi.org/10.1038/s41588-023-01638-x](https://doi.org/10.1038/s41588-023-01638-x)\u003Cbr>Inherited polygenic effects on common hematological traits influence clonal selection onJAK2V617Fand the development of myeloproliferative neoplasms |  |  |  |\n| Received: 22 December 2022\u003Cbr>Accepted: 1 December 2023\u003Cbr>Published online: 17 January 2024  Check for updates | Jing Guo  1,2, Klaudia Walter  1, Pedro M. Quiros1,3,4, Muxin Gu1,\u003Cbr>E. Joanna Baxter4, John Danesh1,2,5,6,7, Emanuele Di Angelantonio2,5,6,7,8,\u003Cbr>David Roberts2,9, Paola Guglielmelli  10, Claire N. Harrison11, Anna L. Godfrey12, Anthony R. Green3,13, GeorgeS. Vassiliou  3,13, Dragana Vuckovic1,2,14,15,\u003Cbr>Jyoti Nangalia  1,3,12,13,15 & Nicole Soranzo  1,2,6,8,13,15\u003Cbr>Myeloproliferative neoplasms (MPNs) are chronic cancers characterized by overproduction of mature blood cells. Their causative somatic mutations, for example,JAK2V617F, are common in the population, yet only a minority of carriers develop MPN. Here we showthatthe inherited polygenic loci that underlie common hematological traits influenceJAK2V617F clonal expansion. We identify polygenic risk scores (PGSs) formonocyte count and plateletcrit as new risk factors forJAK2V617F positivity. PGSs for several hematological traits influenced the risk of different MPN subtypes, with low PGSs for two platelet traits also showing protective effects inJAK2V617F carriers, making them two to three times less likely to have essential thrombocythemia than carriers with high PGSs. We observed that extreme hematological PGSs may contribute toan MPN diagnosis in the absence of somatic driver mutations. Our study showcases how polygenic backgrounds underlying common hematological traits influence both clonal selection on somatic mutations and the subsequent phenotype of cancer. |  |  |\n| Myeloproliferative neoplasms (MPNs) are rare chronic hematological cancers characterized by the overproduction of mature blood cells leading to elevated blood cell parameters. They are typically driven by somatically mutatedJAK2-mediated, calreticulin (CALR)-mediated |  | or MPL-mediated clonal expansion1.JAK2 mutations are found in both polycythemia vera (PV) and essential thrombocythemia (ET), which are distinct but overlapping MPNs characterized by increased numbers of red blood cells and platelets, respectively. Mutant JAK2 is commonly |  |\n| 1Wellcome Sanger Institute, Hinxton, UK. 2National Institute for Health Research Blood and Transplant Research Unit in Donor Health and Genomics, University of Cambridge, Cambridge, UK. 3Wellcome–MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, UK. 4Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain. 5British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. 6British Heart Foundation Centre of Research Excellence, University of Cambridge, Cambridge, UK. 7Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Cambridge, UK. 8Fondazione Human Technopole, Milan, Italy. 9NHS Blood and Transplant–Oxford Centre, John Radcliffe Hospital and Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK. 10Department of Experimental and Clinical Medicine, Center for Research and Innovation of Myeloproliferative Neoplasms (CRIMM), AOU Careggi, University of Florence, Florence, Italy. 11Department of Haematology, Guy’s and St Thomas’ NHS Foundation Trust, London, UK. 12Cambridge University Hospitals NHS Trust, Cambridge, UK. 13Department of Haematology, University of Cambridge, Cambridge, UK. 14Department of Epidemiology and Biostatistics, School of Public Health, Faculty of Medicine, Imperial College London, London, UK. 15These authors jointly supervised this work: Dragana Vuckovic, Jyoti Nangalia, Nicole So","cbCaibjlqv2VYrM3","https://ap.wps.com/l/cbCaibjlqv2VYrM3","pdf",2000467,16,"English","# Overview\n## JAK2(V617F) and inherited polygenic influences\n## Polygenic risk scores and MPN subtype risk\n## Platelet traits and protection against essential thrombocythemia\n## Extreme polygenic profiles and diagnosis without driver mutations\n# Figure 1\n## Germline polygenic risk and association with JAK2(V617F) positivity","[{\"question\":\"What does the study conclude about inherited polygenic effects and JAK2(V617F)?\",\"answer\":\"Inherited polygenic loci that underlie common hematological traits influence the expansion of JAK2(V617F) clones and relate to downstream MPN phenotype development.\"},{\"question\":\"Which polygenic risk scores are identified as new risk factors for JAK2(V617F) positivity?\",\"answer\":\"Polygenic risk scores for monocyte count and plateletcrit are reported as new risk factors for JAK2(V617F) positivity.\"},{\"question\":\"How do low polygenic risk scores affect essential thrombocythemia among JAK2(V617F) carriers?\",\"answer\":\"Low polygenic scores for two platelet traits show protective effects, making carriers two to three times less likely to have essential thrombocythemia than carriers with high polygenic scores.\"}]","Inherited polygenic effects on common hematological traits influence clonal selection on JAK2(V617F) | PDF",1789987115]