ArticleWorld journal of urology2026
Unveiling novel susceptibility genes for kidney stone disease by a cross-tissue transcriptome-wide association study.
Article in World journal of urology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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Who cites it
1 citing paper in PubMed.
- Unveiling novel susceptibility genes for sarcoidosis by a cross-tissue transcriptome-wide association study.Sarcoidosis, vasculitis, and diffuse lung diseases : official journal of WASOG · 2026Article
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1 author.
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Abstract
purposeKidney stone disease has a strong but incompletely understood genetic component. Traditional genome-wide association studies (GWAS) mostly uncover non-coding variants whose target genes remain ambiguous. Integrating transcriptome-wide association studies (TWAS) with post-GWAS analyses can pinpoint the genes through which these variants act.
methodUsing GWAS summary statistics from 12,999 cases and 486,185 controls (FinnGen R12), we performed cross-tissue TWAS with UTMOST and single-tissue TWAS with FUSION across 49 GTEx v8 tissues. Significant findings were independently replicated using an external GWAS dataset. Genes significant in both screens were refined by MAGMA gene-level tests, Mendelian randomization (MR), Bayesian colocalization (COLOC), GeneMANIA network analysis and a comprehensive PheWAS in 484,111 UK Biobank participants.
resultsTWAS identified 32 cross-tissue and 354 single-tissue significant genes; replication analysis confirmed 11 and 147 overlapping genes, respectively. The intersection of five methods yielded USP40, NLRC4, GCAT, and UGT8. MR and COLOC supported correlations for all four: USP40, GCAT and UGT8 conferred risk, whereas NLRC4 was protective. Network analyses placed these genes in immune regulation, amino-acid metabolism and glucuronidation pathways. PheWAS revealed pleiotropic associations with metabolic, genitourinary and neurological traits.
conclusionsIntegrative cross-tissue TWAS uncovers four novel, biologically plausible susceptibility genes for kidney stone disease. These findings refine the genetic architecture of nephrolithiasis and nominate tractable biomarkers and therapeutic targets for precision prevention.
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