# Genomics of glomerular disease

> **NIH NIH RC2** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2022 · $870,143

## Abstract

Abstract:
Glomerular disorders represent the third-most common cause of end-stage renal disease after diabetes and
hypertension. IgA nephropathy (IgAN), focal segmental glomerulosclerosis (FSGS), membranous nephropathy
(MN) and minimal change disease (MCD) account for the majority of idiopathic glomerular diseases. Recent
genetic studies have identified several genetic loci for these disorders and have begun to identify critical
molecular pathways involved in their pathogenesis. However, well-designed and adequately powered genetic
association studies are still missing for most glomerular disease types. Moreover, the field is faced with major
challenges, including the need to validate the new loci across diverse patient cohorts, understand dysregulated
pathways downstream of risk alleles and their consequences on clinical outcomes, define disease-specificity
and interactions of risk alleles, and place their functional consequences within a coherent biological network.
Such insights can then be translated into clinical benefits, including reliable biomarkers, effective strategies for
screening and prevention, and rational selection of potential therapeutic targets. This proposal will address the
above challenges by aiming to discover, validate, and fine-map known and novel genetic susceptibility loci by
collaborative genetic studies. This will include a pioneering partnership with AstraZeneca and Columbia's
Institute for Genomic Medicine to perform whole genome sequencing (WGS) of 4,000 cases of glomerular
disease, including the entire CureGN study, the largest prospective cohort of patients with glomerular disorders.
This will be followed by international meta-analyses and genetic validation studies in additional 26,000 cases of
biopsy-confirmed primary glomerular disorders. Next, we will aim to discover precise pathogenic mechanisms
underpinning each of the new genetic loci using systems genetics studies in the CureGN cohort. We will
integrate the genetic data with blood transcriptomic studies and clinico-pathologic analyses to identify the key
molecular disease drivers and their clinical and histopathologic consequences. Our studies will leverage the
largest investment of NIDDK in glomerular diseases to refine the molecular pathogenesis and will be critical in
defining targets for novel therapeutic interventions.

## Key facts

- **NIH application ID:** 10413152
- **Project number:** 5RC2DK116690-05
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Krzysztof Kiryluk
- **Activity code:** RC2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $870,143
- **Award type:** 5
- **Project period:** 2018-06-14 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10413152

## Citation

> US National Institutes of Health, RePORTER application 10413152, Genomics of glomerular disease (5RC2DK116690-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10413152. Licensed CC0.

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