AI Article Synopsis

  • IgA nephropathy (IgAN) is a serious kidney disease linked to IgA buildup, and a large study identified 30 genetic risk factors associated with it.
  • Fourteen new loci were discovered that suggest a connection between genetic influences and abnormal IgA levels.
  • The research highlights inflammation-related pathways and potential drug targets, revealing that higher genetic risk scores are tied to earlier kidney failure.

Article Abstract

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.

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Source
http://dx.doi.org/10.1038/s41588-023-01422-xDOI Listing

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