Deciphering the genetics and mechanisms of predisposition to multiple myeloma
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378041%3A_____%2F24%3A00597551" target="_blank" >RIV/68378041:_____/24:00597551 - isvavai.cz</a>
Alternative codes found
RIV/61988987:17110/24:A25039MW RIV/00216208:11140/24:10482801 RIV/00843989:_____/24:E0111065
Result on the web
<a href="https://www.nature.com/articles/s41467-024-50932-7" target="_blank" >https://www.nature.com/articles/s41467-024-50932-7</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s41467-024-50932-7" target="_blank" >10.1038/s41467-024-50932-7</a>
Alternative languages
Result language
angličtina
Original language name
Deciphering the genetics and mechanisms of predisposition to multiple myeloma
Original language description
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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30204 - Oncology
Result continuities
Project
—
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Nature Communications
ISSN
2041-1723
e-ISSN
2041-1723
Volume of the periodical
15
Issue of the periodical within the volume
1
Country of publishing house
GB - UNITED KINGDOM
Number of pages
15
Pages from-to
6644
UT code for WoS article
001284820100008
EID of the result in the Scopus database
2-s2.0-85200470126