Haplotype analysis identifies functional elements in monoclonal gammopathy of unknown significance
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378041%3A_____%2F24%3A00597687" target="_blank" >RIV/68378041:_____/24:00597687 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11140/24:10483331 RIV/61988987:17110/24:A25039MS RIV/00216208:11110/24:10483331 RIV/00843989:_____/24:E0111066
Result on the web
<a href="https://www.nature.com/articles/s41408-024-01121-8" target="_blank" >https://www.nature.com/articles/s41408-024-01121-8</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s41408-024-01121-8" target="_blank" >10.1038/s41408-024-01121-8</a>
Alternative languages
Result language
angličtina
Original language name
Haplotype analysis identifies functional elements in monoclonal gammopathy of unknown significance
Original language description
Genome-wide association studies (GWASs) based on common single nucleotide polymorphisms (SNPs) have identified several loci associated with the risk of monoclonal gammopathy of unknown significance (MGUS), a precursor condition for multiple myeloma (MM). We hypothesized that analyzing haplotypes might be more useful than analyzing individual SNPs, as it could identify functional chromosomal units that collectively contribute to MGUS risk. To test this hypothesis, we used data from our previous GWAS on 992 MGUS cases and 2910 controls from three European populations. We identified 23 haplotypes that were associated with the risk of MGUS at the genome-wide significance level (p < 5 x 10(-8)) and showed consistent results among all three populations. In 10 genomic regions, strong promoter, enhancer and regulatory element-related histone marks and their connections to target genes as well as genome segmentation data supported the importance of these regions in MGUS susceptibility. Several associated haplotypes affected pathways important for MM cell survival such as ubiquitin-proteasome system (RNF186, OTUD3), PI3K/AKT/mTOR (HINT3), innate immunity (SEC14L1, ZBP1), cell death regulation (BID) and NOTCH signaling (RBPJ). These pathways are important current therapeutic targets for MM, which may highlight the advantage of the haplotype approach homing to functional units.
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
Result was created during the realization of more than one project. More information in the Projects tab.
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
Blood Cancer Journal
ISSN
2044-5385
e-ISSN
2044-5385
Volume of the periodical
14
Issue of the periodical within the volume
1
Country of publishing house
GB - UNITED KINGDOM
Number of pages
12
Pages from-to
140
UT code for WoS article
001295007500002
EID of the result in the Scopus database
2-s2.0-85201603885