Genome-wide association analyses define pathogenic signaling pathways and prioritize drug targets for IgA nephropathy
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064165%3A_____%2F23%3A10466343" target="_blank" >RIV/00064165:_____/23:10466343 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11110/23:10466343
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=jdDy-KNBYC" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=jdDy-KNBYC</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s41588-023-01422-x" target="_blank" >10.1038/s41588-023-01422-x</a>
Alternative languages
Result language
angličtina
Original language name
Genome-wide association analyses define pathogenic signaling pathways and prioritize drug targets for IgA nephropathy
Original language description
Genome-wide association analyses identify 30 risk loci for IgA nephropathy. Functional annotations of putative causal genes converge on inflammatory signaling pathways and cytokine ligand-receptor pairs, prioritizing potential new drug targets. IgA nephropathy (IgAN) is a progressive form of kidney disease defined by glomerular deposition of IgA. Here we performed a genome-wide association study of 10,146 kidney-biopsy-diagnosed IgAN cases and 28,751 controls across 17 international cohorts. We defined 30 genome-wide significant risk loci explaining 11% of disease risk. A total of 16 loci were new, including TNFSF4/TNFSF18, REL, CD28, PF4V1, LY86, LYN, ANXA3, TNFSF8/TNFSF15, REEP3, ZMIZ1, OVOL1/RELA, ETS1, IGH, IRF8, TNFRSF13B and FCAR. The risk loci were enriched in gene orthologs causing abnormal IgA levels when genetically manipulated in mice. We also observed a positive genetic correlation between IgAN and serum IgA levels. High polygenic score for IgAN was associated with earlier onset of kidney failure. In a comprehensive functional annotation analysis of candidate causal genes, we observed convergence of biological candidates on a common set of inflammatory signaling pathways and cytokine ligand-receptor pairs, prioritizing potential new drug targets.
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
30217 - Urology and nephrology
Result continuities
Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2023
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Nature Genetics
ISSN
1061-4036
e-ISSN
1546-1718
Volume of the periodical
55
Issue of the periodical within the volume
7
Country of publishing house
US - UNITED STATES
Number of pages
32
Pages from-to
1091-1105
UT code for WoS article
001012076800002
EID of the result in the Scopus database
2-s2.0-85162272555