Show simple item record

dc.contributor.authorBarratt, Jonathan
dc.date.accessioned2023-07-31T15:27:51Z
dc.date.available2023-07-31T15:27:51Z
dc.date.issued2023-06-19
dc.identifier.citationKiryluk, K., Sanchez-Rodriguez, E., Zhou, X. J., Zanoni, F., Liu, L., Mladkova, N., Khan, A., Marasa, M., Zhang, J. Y., Balderes, O., Sanna-Cherchi, S., Bomback, A. S., Canetta, P. A., Appel, G. B., Radhakrishnan, J., Trimarchi, H., Sprangers, B., Cattran, D. C., Reich, H., Pei, Y., … Gharavi, A. G. (2023). Genome-wide association analyses define pathogenic signaling pathways and prioritize drug targets for IgA nephropathy. Nature genetics, 55(7), 1091–1105. https://doi.org/10.1038/s41588-023-01422-xen_US
dc.identifier.other10.1038/s41588-023-01422-x
dc.identifier.urihttp://hdl.handle.net/20.500.12904/17414
dc.description.abstractIgA 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.
dc.description.urihttps://www.nature.com/articles/s41588-023-01422-xen_US
dc.language.isoenen_US
dc.titleGenome-wide association analyses define pathogenic signaling pathways and prioritize drug targets for IgA nephropathyen_US
dc.typeArticleen_US
rioxxterms.funderDefault funderen_US
rioxxterms.identifier.projectDefault projecten_US
rioxxterms.versionNAen_US
rioxxterms.versionofrecordhttps://doi.org/10.1038/s41588-023-01422-xen_US
rioxxterms.typeJournal Article/Reviewen_US
refterms.panelUnspecifieden_US
html.description.abstractIgA 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.en_US
rioxxterms.funder.project94a427429a5bcfef7dd04c33360d80cden_US


This item appears in the following Collection(s)

Show simple item record