Kidney Week 2025 Annual Meeting-Genetics of Complex Kidney Traits

Video Transcription

Video Summary

The session on genetics of complex kidney traits featured multiple talks spanning GWAS, multi-omics atlases, gene regulation, and translational genetics.<br /><br />A Columbia University team presented the largest GWAS of idiopathic nephrotic syndrome (INS) to date (7,610 cases, 29,000 controls), stratified by age of onset and steroid response. Pediatric steroid-sensitive INS showed 17 genome-wide significant loci (nine new), mostly near immune genes, reinforcing immune dysregulation. Adult steroid-sensitive INS showed a strong but different HLA haplotype and only partial overlap with pediatric signals. In pediatric steroid-resistant INS, removing Mendelian/APOL1 “solved” cases strengthened HLA associations, suggesting immune predisposition in non-Mendelian disease. Adult steroid-resistant INS showed few strong common-variant signals, consistent with high heterogeneity.<br /><br />Using Million Veteran Program data, a Vanderbilt group analyzed renal cell carcinoma (RCC) genetics across ancestries and subtypes. They identified known RCC loci in Europeans and, in African ancestry, found both known signals (including VHL) and two potentially novel inflammatory/innate immunity genes (IL17RC, IREC2). Regulatory (non-coding) variants were emphasized, with planned transcriptomic/proteomic follow-up.<br /><br />A WashU team described building a pediatric multiomic and spatial kidney atlas (snRNA+snATAC, spatial transcriptomics, CUT&RUN). They identified maturation-linked expression changes and a potential postnatal progenitor-like cluster between parietal epithelial cells and podocytes. Trajectory and regulatory analyses nominated transcription factors (e.g., NFE2L1) potentially driving podocyte maturation, with iPSC-based validation underway.<br /><br />Additional talks covered disease-specific blood QTL maps in glomerular disorders, allele-specific expression differences between glomeruli and tubulointerstitium linked to outcomes, APOL1 alanine-scanning to map cytotoxic and inhibitor-sensitive regions, proteome-wide Mendelian randomization for kidney drug targets, improved eGFR polygenic prediction by removing biomarker-specific genetics, and evidence that vitamin D supplementation increases kidney stone risk in heterozygous SLC34A3 or CYP24A1 carriers.

Asset Subtitle

Moderator(s): Hongbo Liu, Francesca Zanoni

Presentation(s):

Genome-Wide Association Study for Idiopathic Nephrotic Syndrome Identifies Susceptibility Loci Across the Lifespan, Response to Therapy, and Genetic Ancestry - Tze Yin Lim
Genetic Architecture of Renal Cell Cancer (RCC) in the Million Veteran Program Highlights Differences by Ancestry and Papillary Subtype - Fatih Mamak
Pediatric Multiomic and Spatial Kidney Atlas Identifies Regulatory Networks Driving Postnatal Kidney Maturation - Katerina Trachtova
Atlas of Glomerular Disease-Specific Genetic Effects on Gene Regulation in Blood Empowers New Gene Discovery Studies - Lili Liu
Proportion of Allele-Specific Expression Is Different in Glomeruli and Tubulointerstitium of Proteinuric Kidneys and Correlated to Disease Progression - Ana Onuchic-Whitford
Functional Mapping of APOL1 G1 Reveals Key Regions Modulating Cytotoxicity and Inhibitor Sensitivity - Varsha Neelakantan
Integrative Proteome- and Phenome-Wide Study Uncovers Causal Protein Drivers and Drug Targets for Kidney Disease Subtypes - Jefferson Triozzi
Improving Polygenic Risk Prediction of Kidney Function by Removing Biomarker-Specific Genetics - Jiawen Du
Vitamin D Supplementation in Individuals Heterozygous for SLC34A3 or CYP24A1 Further Increases Nephrolithiasis Risk - Kevin Xu

Note: Continuing education credits are not being offered for this session.

Meta Tag

Date 11/6/2025

Pathway 1 Genetic Diseases and Development

Session ID 519864

Keywords

complex kidney traits

GWAS

idiopathic nephrotic syndrome

steroid-sensitive nephrotic syndrome

steroid-resistant nephrotic syndrome

HLA haplotypes

immune dysregulation

renal cell carcinoma genetics

multi-omics kidney atlas

single-nucleus RNA-seq

spatial transcriptomics

APOL1 variants

Mendelian randomization