Academic Journal
Deciphering the genetics and mechanisms of predisposition to multiple myeloma
| العنوان: | Deciphering the genetics and mechanisms of predisposition to multiple myeloma |
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| المؤلفون: | Went, Molly, Duran-Lozano, Laura, Halldorsson, Gisli H., Gunnell, Andrea, Ugidos-Damboriena, Nerea, Law, Philip, Ekdahl, Ludvig, Sud, Amit, Thorleifsson, Gudmar, Thodberg, Malte, Olafsdottir, Thorunn, Lamarca-Arrizabalaga, Antton, Cafaro, Caterina, Niroula, Abhishek, Ajore, Ram, Lopez de Lapuente Portilla, Aitzkoa, Ali, Zain, Pertesi, Maroulio, Goldschmidt, Hartmut, Stefansdottir, Lilja, Kristinsson, Sigurdur Y., Stacey, Simon N., Love, Thorvardur J., Rognvaldsson, Saemundur, Hajek, Roman, Vodicka, Pavel, Pettersson-Kymmer, Ulrika, Späth, Florentin, Schinke, Carolina, Van Rhee, Frits, Sulem, Patrick, Ferkingstad, Egil, Hjorleifsson Eldjarn, Grimur, Mellqvist, Ulf-Henrik, Jonsdottir, Ingileif, Morgan, Gareth, Sonneveld, Pieter, Waage, Anders, Weinhold, Niels, Thomsen, Hauke, Försti, Asta, Hansson, Markus, Juul-Vangsted, Annette, Thorsteinsdottir, Unnur, Hemminki, Kari, Kaiser, Martin, Rafnar, Thorunn, Stefansson, Kari, Houlston, Richard, Nilsson, Björn |
| بيانات النشر: | UmeÃ¥ universitet, Institutionen för integrativ medicinsk biologi (IMB) UmeÃ¥ universitet, Institutionen för strÃ¥lningsvetenskaper Division of Genetics and Epidemiology, The Institute of Cancer Research, London, United Kingdom Department of Laboratory Medicine, Lund University, Lund, Sweden; Lund Stem Cell Center, Lund University, Lund, Sweden deCODE Genetics/Amgen, Reykjavik, Iceland deCODE Genetics/Amgen, Sturlugata 8, Reykjavik, Iceland Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany Landspitali, National University Hospital of Iceland, Reykjavik, Iceland; Faculty of Medicine, University of Iceland, Reykjavik, Iceland University Hospital Ostrava and University of Ostrava, Ostrava, Czech Republic Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic Myeloma Center, University of Arkansas for Medical Sciences, AR, Little Rock, United States Southern Älvsborg Hospital, BorÃ¥s, Sweden Perlmutter Cancer Center, Langone Health, New York University, NY, New York, United States Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, Netherlands Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany MSB Medical School Berlin, Berlin, Germany German Cancer Research Center (DKFZ), Heidelberg, Germany; Hopp Children’s Cancer Center, Heidelberg, Germany Department of Laboratory Medicine, Lund University, Lund, Sweden; Section of Hematology, Sahlgrenska University Hospital, Gothenburg, Sweden; SkÃ¥ne University Hospital, Lund, Sweden Department of Haematology, University Hospital of Copenhagen at Rigshospitalet, Copenhagen, Denmark deCODE Genetics/Amgen, Reykjavik, Iceland; Faculty of Medicine, University of Iceland, Reykjavik, Iceland German Cancer Research Center (DKFZ), Heidelberg, Germany; Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic deCODE Genetics/Amgen, , Reykjavik, Iceland; Faculty of Medicine, University of Iceland, Reykjavik, Iceland Department of Laboratory Medicine, Lund University, Lund, Sweden; Lund Stem Cell Center, Lund University, Lund, Sweden; Broad Institute, MA, Cambridge, United States |
| سنة النشر: | 2024 |
| المجموعة: | Umeå University: Publications (DiVA) |
| مصطلحات موضوعية: | Medical Genetics, Medicinsk genetik, Cancer and Oncology, Cancer och onkologi |
| الوصف: | Multiple myeloma (MM) is an incurable malignancy of plasma cells. Epidemiological studies indicate a substantial heritable component, but the underlying mechanisms remain unclear. Here, in a genome-wide association study totaling 10,906 cases and 366,221 controls, we identify 35 MM risk loci, 12 of which are novel. Through functional fine-mapping and Mendelian randomization, we uncover two causal mechanisms for inherited MM risk: longer telomeres; and elevated levels of B-cell maturation antigen (BCMA) and interleukin-5 receptor alpha (IL5RA) in plasma. The largest increase in BCMA and IL5RA levels is mediated by the risk variant rs34562254-A at TNFRSF13B. While individuals with loss-of-function variants in TNFRSF13B develop B-cell immunodeficiency, rs34562254-A exerts a gain-of-function effect, increasing MM risk through amplified B-cell responses. Our results represent an analysis of genetic MM predisposition, highlighting causal mechanisms contributing to MM development. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| Relation: | Nature Communications, 2024, 15:1; orcid:0000-0002-0557-9803; orcid:0000-0002-0711-0830; http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-228486; PMID 39103364; Scopus 2-s2.0-85200470126 |
| DOI: | 10.1038/s41467-024-50932-7 |
| الاتاحة: | http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-228486 https://doi.org/10.1038/s41467-024-50932-7 |
| Rights: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.2172AADB |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41467-024-50932-7 |
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