Language
English
Publication Date
7-1-2023
Journal
Nature Genetics
DOI
10.1038/s41588-023-01422-x
PMID
37337107
PMCID
PMC11824687
PubMedCentral® Posted Date
2-13-2025
PubMedCentral® Full Text Version
Author MSS
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.
Keywords
Animals, Mice, Glomerulonephritis, IGA, Genome-Wide Association Study, Immunoglobulin A
Published Open-Access
yes
Recommended Citation
Kiryluk, Krzysztof; Sanchez-Rodriguez, Elena; Zhou, Xu-Jie; et al., "Genome-Wide Association Analyses Define Pathogenic Signaling Pathways and Prioritize Drug Targets for IgA Nephropathy" (2023). Faculty and Staff Publications. 2993.
https://digitalcommons.library.tmc.edu/baylor_docs/2993
Included in
Medical Genetics Commons, Medical Immunology Commons, Nephrology Commons, Pediatrics Commons