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| 001 | 292095 | ||
| 005 | 20241118124022.0 | ||
| 024 | 7 | _ | |a 10.1038/s41467-024-50932-7 |2 doi |
| 024 | 7 | _ | |a pmid:39103364 |2 pmid |
| 024 | 7 | _ | |a altmetric:166027397 |2 altmetric |
| 037 | _ | _ | |a DKFZ-2024-01594 |
| 041 | _ | _ | |a English |
| 082 | _ | _ | |a 500 |
| 100 | 1 | _ | |a Went, Molly |0 0000-0003-3271-975X |b 0 |
| 245 | _ | _ | |a Deciphering the genetics and mechanisms of predisposition to multiple myeloma. |
| 260 | _ | _ | |a [London] |c 2024 |b Nature Publishing Group UK |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1723018807_13786 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
| 336 | 7 | _ | |a JOURNAL_ARTICLE |2 ORCID |
| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 520 | _ | _ | |a 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. |
| 536 | _ | _ | |a 312 - Funktionelle und strukturelle Genomforschung (POF4-312) |0 G:(DE-HGF)POF4-312 |c POF4-312 |f POF IV |x 0 |
| 588 | _ | _ | |a Dataset connected to CrossRef, PubMed, , Journals: inrepo02.dkfz.de |
| 650 | _ | 7 | |a B-Cell Maturation Antigen |2 NLM Chemicals |
| 650 | _ | 7 | |a TNFRSF13B protein, human |2 NLM Chemicals |
| 650 | _ | 7 | |a Transmembrane Activator and CAML Interactor Protein |2 NLM Chemicals |
| 650 | _ | 2 | |a Multiple Myeloma: genetics |2 MeSH |
| 650 | _ | 2 | |a Humans |2 MeSH |
| 650 | _ | 2 | |a Genetic Predisposition to Disease |2 MeSH |
| 650 | _ | 2 | |a Genome-Wide Association Study |2 MeSH |
| 650 | _ | 2 | |a B-Cell Maturation Antigen: genetics |2 MeSH |
| 650 | _ | 2 | |a Polymorphism, Single Nucleotide |2 MeSH |
| 650 | _ | 2 | |a Mendelian Randomization Analysis |2 MeSH |
| 650 | _ | 2 | |a B-Lymphocytes: immunology |2 MeSH |
| 650 | _ | 2 | |a B-Lymphocytes: metabolism |2 MeSH |
| 650 | _ | 2 | |a Case-Control Studies |2 MeSH |
| 650 | _ | 2 | |a Transmembrane Activator and CAML Interactor Protein: genetics |2 MeSH |
| 650 | _ | 2 | |a Male |2 MeSH |
| 650 | _ | 2 | |a Telomere: genetics |2 MeSH |
| 700 | 1 | _ | |a Duran-Lozano, Laura |b 1 |
| 700 | 1 | _ | |a Halldorsson, Gisli H |0 0000-0001-7067-9862 |b 2 |
| 700 | 1 | _ | |a Gunnell, Andrea |0 0000-0001-5162-5391 |b 3 |
| 700 | 1 | _ | |a Ugidos-Damboriena, Nerea |b 4 |
| 700 | 1 | _ | |a Law, Philip |0 0000-0001-9663-4611 |b 5 |
| 700 | 1 | _ | |a Ekdahl, Ludvig |b 6 |
| 700 | 1 | _ | |a Sud, Amit |0 0000-0002-6133-0164 |b 7 |
| 700 | 1 | _ | |a Thorleifsson, Gudmar |0 0000-0003-4623-9087 |b 8 |
| 700 | 1 | _ | |a Thodberg, Malte |0 0000-0001-6244-3841 |b 9 |
| 700 | 1 | _ | |a Olafsdottir, Thorunn |0 0000-0001-5454-938X |b 10 |
| 700 | 1 | _ | |a Lamarca-Arrizabalaga, Antton |0 0009-0008-3426-2347 |b 11 |
| 700 | 1 | _ | |a Cafaro, Caterina |b 12 |
| 700 | 1 | _ | |a Niroula, Abhishek |0 0000-0002-5904-0635 |b 13 |
| 700 | 1 | _ | |a Ajore, Ram |b 14 |
| 700 | 1 | _ | |a Lopez de Lapuente Portilla, Aitzkoa |b 15 |
| 700 | 1 | _ | |a Ali, Zain |b 16 |
| 700 | 1 | _ | |a Pertesi, Maroulio |0 0000-0002-4869-8925 |b 17 |
| 700 | 1 | _ | |a Goldschmidt, Hartmut |b 18 |
| 700 | 1 | _ | |a Stefansdottir, Lilja |b 19 |
| 700 | 1 | _ | |a Kristinsson, Sigurdur Y |b 20 |
| 700 | 1 | _ | |a Stacey, Simon N |0 0000-0002-4732-7380 |b 21 |
| 700 | 1 | _ | |a Love, Thorvardur J |b 22 |
| 700 | 1 | _ | |a Rognvaldsson, Saemundur |b 23 |
| 700 | 1 | _ | |a Hajek, Roman |0 0000-0001-6955-6267 |b 24 |
| 700 | 1 | _ | |a Vodicka, Pavel |b 25 |
| 700 | 1 | _ | |a Pettersson-Kymmer, Ulrika |0 0000-0002-0557-9803 |b 26 |
| 700 | 1 | _ | |a Späth, Florentin |b 27 |
| 700 | 1 | _ | |a Schinke, Carolina |0 0000-0002-2699-1741 |b 28 |
| 700 | 1 | _ | |a Van Rhee, Frits |0 0000-0001-9959-1282 |b 29 |
| 700 | 1 | _ | |a Sulem, Patrick |0 0000-0001-7123-6123 |b 30 |
| 700 | 1 | _ | |a Ferkingstad, Egil |0 0000-0001-8090-7988 |b 31 |
| 700 | 1 | _ | |a Hjorleifsson Eldjarn, Grimur |0 0000-0002-9580-6685 |b 32 |
| 700 | 1 | _ | |a Mellqvist, Ulf-Henrik |b 33 |
| 700 | 1 | _ | |a Jonsdottir, Ingileif |0 0000-0001-8339-150X |b 34 |
| 700 | 1 | _ | |a Morgan, Gareth |0 0000-0002-4271-6360 |b 35 |
| 700 | 1 | _ | |a Sonneveld, Pieter |b 36 |
| 700 | 1 | _ | |a Waage, Anders |0 0000-0001-9072-1220 |b 37 |
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| 700 | 1 | _ | |a Hansson, Markus |0 0000-0002-7715-4548 |b 41 |
| 700 | 1 | _ | |a Juul-Vangsted, Annette |0 0000-0002-2131-731X |b 42 |
| 700 | 1 | _ | |a Thorsteinsdottir, Unnur |b 43 |
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| 700 | 1 | _ | |a Kaiser, Martin |0 0000-0002-3677-4804 |b 45 |
| 700 | 1 | _ | |a Rafnar, Thorunn |0 0000-0003-0491-7046 |b 46 |
| 700 | 1 | _ | |a Stefansson, Kari |0 0000-0003-1676-864X |b 47 |
| 700 | 1 | _ | |a Houlston, Richard |0 0000-0002-5268-0242 |b 48 |
| 700 | 1 | _ | |a Nilsson, Björn |0 0000-0001-5542-0254 |b 49 |
| 773 | _ | _ | |a 10.1038/s41467-024-50932-7 |g Vol. 15, no. 1, p. 6644 |0 PERI:(DE-600)2553671-0 |n 1 |p 6644 |t Nature Communications |v 15 |y 2024 |x 2041-1723 |
| 856 | 4 | _ | |u https://inrepo02.dkfz.de/record/292095/files/s41467-024-50932-7.pdf |
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