dc.contributor.author | Went, M | |
dc.contributor.author | Duran-Lozano, L | |
dc.contributor.author | Halldorsson, GH | |
dc.contributor.author | Gunnell, A | |
dc.contributor.author | Ugidos-Damboriena, N | |
dc.contributor.author | Law, P | |
dc.contributor.author | Ekdahl, L | |
dc.contributor.author | Sud, A | |
dc.contributor.author | Thorleifsson, G | |
dc.contributor.author | Thodberg, M | |
dc.contributor.author | Olafsdottir, T | |
dc.contributor.author | Lamarca-Arrizabalaga, A | |
dc.contributor.author | Cafaro, C | |
dc.contributor.author | Niroula, A | |
dc.contributor.author | Ajore, R | |
dc.contributor.author | Lopez de Lapuente Portilla, A | |
dc.contributor.author | Ali, Z | |
dc.contributor.author | Pertesi, M | |
dc.contributor.author | Goldschmidt, H | |
dc.contributor.author | Stefansdottir, L | |
dc.contributor.author | Kristinsson, SY | |
dc.contributor.author | Stacey, SN | |
dc.contributor.author | Love, TJ | |
dc.contributor.author | Rognvaldsson, S | |
dc.contributor.author | Hajek, R | |
dc.contributor.author | Vodicka, P | |
dc.contributor.author | Pettersson-Kymmer, U | |
dc.contributor.author | Späth, F | |
dc.contributor.author | Schinke, C | |
dc.contributor.author | Van Rhee, F | |
dc.contributor.author | Sulem, P | |
dc.contributor.author | Ferkingstad, E | |
dc.contributor.author | Hjorleifsson Eldjarn, G | |
dc.contributor.author | Mellqvist, U-H | |
dc.contributor.author | Jonsdottir, I | |
dc.contributor.author | Morgan, G | |
dc.contributor.author | Sonneveld, P | |
dc.contributor.author | Waage, A | |
dc.contributor.author | Weinhold, N | |
dc.contributor.author | Thomsen, H | |
dc.contributor.author | Försti, A | |
dc.contributor.author | Hansson, M | |
dc.contributor.author | Juul-Vangsted, A | |
dc.contributor.author | Thorsteinsdottir, U | |
dc.contributor.author | Hemminki, K | |
dc.contributor.author | Kaiser, M | |
dc.contributor.author | Rafnar, T | |
dc.contributor.author | Stefansson, K | |
dc.contributor.author | Houlston, R | |
dc.contributor.author | Nilsson, B | |
dc.date.accessioned | 2024-08-09T11:09:33Z | |
dc.date.available | 2024-08-09T11:09:33Z | |
dc.date.issued | 2024-08-05 | |
dc.identifier.citation | Nature Communications, 2024, | |
dc.identifier.issn | 2041-1723 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/6346 | |
dc.identifier.eissn | 2041-1723 | |
dc.identifier.eissn | 2041-1723 | |
dc.description.abstract | 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. | |
dc.language.iso | eng | |
dc.publisher | Springer Science and Business Media LLC | |
dc.relation.ispartof | Nature Communications | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.title | Deciphering the genetics and mechanisms of predisposition to multiple myeloma. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2024-07-24 | |
dc.date.updated | 2024-08-06T02:25:15Z | |
rioxxterms.version | VoR | |
rioxxterms.licenseref.startdate | 2024-08-05 | |
rioxxterms.type | Journal Article/Review | |
pubs.organisational-group | ICR | |
pubs.organisational-group | ICR/Primary Group | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions/Genetics and Epidemiology | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Cancer Genomics | |
pubs.organisational-group | ICR/Students | |
pubs.organisational-group | ICR/Students/PhD and MPhil | |
pubs.organisational-group | ICR/Students/PhD and MPhil/14/15 Starting Cohort | |
pubs.publication-status | Published | |
icr.researchteam | Cancer Genomics | |
dc.contributor.icrauthor | Went, Molly | |
dc.contributor.icrauthor | Gunnell, Andrea | |
dc.contributor.icrauthor | Law, Philip | |
dc.contributor.icrauthor | Sud, Amit | |
dc.contributor.icrauthor | Kaiser, Martin | |
dc.contributor.icrauthor | Houlston, Richard | |
icr.provenance | Deposited by Dr Amit Sud on 2024-08-06. Deposit type is initial. No. of files: 1. Files: s41467-024-50932-7.pdf | |