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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

  • Czech description

Classification

  • Type

    J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database

  • CEP classification

  • OECD FORD branch

    30217 - Urology and nephrology

Result continuities

  • Project

  • 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