Cross-Species Comparison between Mouse Kidney Multi-Omics and Human Genome-Wide Association Studies Highlights Molecular Features Associated with Oxalate Nephropathy

This study sought to identify new pathogenetic molecules linked to urolithiasis through multi-omics analysis of a urolithiasis mouse model's kidneys and human genome-wide association analysis (GWAS). In the multi-omics analysis of urolithiasis mouse kidneys using RNA-seq, whole cell proteome, and phosphoproteome, we identified 1,173 genes, 342 proteins, and 516 phosphorylated peptides which were differentially expressed (DE) when comparing model with control mice.

We employed large-scale urolithiasis GWAS resources from BioBank Japan, UK Biobank, and FinnGen through a meta-analysis, which provided 343 urolithiasis-related genes by gene enrichment analysis. Integrating the results of mouse and human analyses, we identified 46 urolithiasis-associated candidate molecules shared across species. We then further validated relevance of these 46 molecules in human urolithiasis.