Kidney Week 2025 Annual Meeting-Genetics of Complex Kidney Traits, Big Data, and Multi-Omics

Video Transcription

Video Summary

This recorded ASN Kidney Week session featured four talks on genetic and genomic approaches to kidney traits and disease, followed by audience Q&A.<br /><br />Matthias Wuttke (CKDGen) reviewed the CKDGen consortium’s large multi-ancestry GWAS meta-analyses (>3.5M participants across six ancestries) for eGFR, UACR, and serum urate. He described a harmonized, automated pipeline and hierarchical meta-analysis (within-ancestry, then multi-ancestry) designed to retain ancestry-specific signals while boosting discovery. CKDGen identified hundreds of associated genomic regions (e.g., ~700 for eGFR) and thousands of independent signals, covering a large fraction of the genome. He highlighted locus-to-gene prioritization integrating proximity, variant impact, eQTL/pQTL colocalization, and LD, and showed how multi-ancestry fine-mapping (multi-SuSiE) yields smaller credible sets. Functional follow-up implicated CHD7 in glomerular barrier biology using Drosophila nephrocyte experiments.<br /><br />Gabriel Loeb discussed “post-GWAS” steps: identifying causal regulatory variants and their target genes. Using single-cell ATAC-seq, his group found kidney function heritability is enriched in regulatory elements active in tubular epithelial cells (and to a lesser extent podocytes). Machine-learning and enhancer assays helped pinpoint functional variants. A CRISPR interference + single-cell RNA-seq “CRISPR-QTL” screen in primary human tubule cells linked fine-mapped enhancers to regulated genes, often at long distances, complementing and extending eQTL approaches.<br /><br />Nita Limdi covered polygenic risk scores (PRS) for CKD and implementation via the eMERGE network, emphasizing reduced PRS portability across ancestries and the need for diverse datasets. She described returning genome-informed risk reports in clinical settings and planned analyses of downstream care changes and outcomes.<br /><br />Tanika Kelly shifted to somatic variation, focusing on clonal hematopoiesis of indeterminate potential (CHIP). She summarized evidence linking CHIP—especially non-DNMT3A subtypes like TET2/JAK2—to eGFR decline, AKI, and CKD progression, supported by epidemiology and mouse models suggesting inflammatory mechanisms and potential cytokine-targeted interventions. Q&A addressed CHIP transplantation questions, germline predisposition to CHIP, and integrating cell-type specificity into functional genomics.

Asset Subtitle

Moderator(s): Matthew Lanktree, Matt Sampson

Presentation(s):

Global Discovery Genome-Wide Association Studies Meta-Analyses for Kidney Traits - Matthias Wuttke
Post Genome-Wide Association Studies of Kidney Risk Loci - Gabriel Loeb
Polygenic Risk Scores in Nephrology and Beyond - Nita Limdi
Clonal Hematopoiesis of Indeterminate Potential (CHIP) and Kidney Diseases - Tanika Kelly

Meta Tag

Date 11/8/2025

Pathway 1 Genetic Diseases and Development

Session ID 507329

Keywords

ASN Kidney Week

CKDGen consortium

multi-ancestry GWAS meta-analysis

eGFR genetics

UACR association

serum urate loci

locus-to-gene prioritization

multi-ancestry fine-mapping

single-cell ATAC-seq kidney

tubular epithelial regulatory elements

CRISPR interference CRISPR-QTL

polygenic risk scores CKD eMERGE

clonal hematopoiesis CHIP kidney disease