Search for AL amyloidosis risk factors using Mendelian randomization
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11140%2F21%3A10430373" target="_blank" >RIV/00216208:11140/21:10430373 - isvavai.cz</a>
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=OIry6-c.sN" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=OIry6-c.sN</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1182/bloodadvances.2021004423" target="_blank" >10.1182/bloodadvances.2021004423</a>
Alternative languages
Result language
angličtina
Original language name
Search for AL amyloidosis risk factors using Mendelian randomization
Original language description
In amyloid light chain (AL) amyloidosis, amyloid fibrils derived from immunoglobulin light chain are deposited in many organs, interfering with their function. The etiology of AL amyloidosis is poorly understood. Summary data from genome-wide association studies (GWASs) of multiple phenotypes can be exploited by Mendelian randomization (MR) methodology to search for factors influencing AL amyloidosis risk. We performed a 2-sample MR analyzing 72 phenotypes, proxied by 3461 genetic variants, and summary genetic data from a GWAS of 1129 AL amyloidosis cases and 7589 controls. Associations with a Bonferroni-defined significance level were observed for genetically predicted increased monocyte counts (P = 3.8 x 10(-4)) and the tumor necrosis factor receptor superfamily member 17 (TNFRSF17) gene (P = 3.4 x 10(-5)). Two other associations with the TNFRSF (members 6 and 19L) reached a nominal significance level. The association between genetically predicted decreased fibrinogen levels may be related to roles of fibrinogen other than blood clotting. be related to its nonhemostatic role. It is plausible that a causal relationship with monocyte concentration could be explained by selection of a light chain-producing clone during progression of monoclonal gammopathy of unknown significance toward AL amyloidosis. Because TNFRSF proteins have key functions in lymphocyte biology, it is entirely plausible that they offer a potential link to AL amyloidosis pathophysiology. Our study provides insight into AL amyloidosis etiology, suggesting high circulating levels of monocytes and TNFRSF proteins as risk factors.
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
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Continuities
R - Projekt Ramcoveho programu EK
Others
Publication year
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Blood Advances
ISSN
2473-9529
e-ISSN
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Volume of the periodical
5
Issue of the periodical within the volume
13
Country of publishing house
US - UNITED STATES
Number of pages
7
Pages from-to
2725-2731
UT code for WoS article
000672759900006
EID of the result in the Scopus database
2-s2.0-85110153087