# Rare variant analysis of glomerulonephritis

> **NIH NIH K01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $151,610

## Abstract

PROJECT SUMMARY
IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. IgAN is a progressive
disease characterized by a gradually decreasing glomerular filtration rate (GFR), which results in end-stage
renal disease (ESRD) in 15% to 20% of patients within 10 years of disease onset. A key observation in our
understanding of the pathogenesis of IgAN is the elevated level of Gd-IgA1 in both serum and glomerular
immune deposits, although the underlying molecular mechanisms are still unclear. This five-year K01
application presents a program for research and training that will support the applicant on a path towards
becoming an NIH-funded independent investigator, focused on studying rare pathogenic variants in patients
with IgAN and single-cell transcriptional landscape according to the level of Gd-IgA1 as an emerging indicator
of biomarker of IgAN. The training plan builds on the candidate's previous training and experience, and
capitalizes on a mentorship team and a research environment to foster development of the candidate's
expertise in (1) clinical domain knowledge to interpret the biological and clinical impact of alterations (2)
development of statistical and computational methods for problems in human genetics (3) applications of
single-cell sequencing for molecular phenotyping of human immune cells relevant to glomerulonephritis and (4)
responsible and ethical conduct in scientific research in human subjects. The research project will conduct
diagnostic annotation of exome sequencing data in 2,500 patients with IgAN based on known Mendelian
causes of kidney disease (Aim #1), discover novel genes associated with IgAN using collapsing methods for
rare variants (2,500 IgAN exome data and > 6,000 control exomes) (Aim #2) and identify cell identity and
transcriptional heterogeneity of IgA producing cells in IgAN patients with high or low Gd-IgA1 compared to
controls using single-cell RNA-seq (Aim #3). Successful completion of this study will improve our
understanding of the role of rare pathogenic variants in IgAN and facilitate clinical diagnosis and personalized
disease-risk profiling. These data along with the research expertise developed through this K01 award will lead
to a successful R01-level proposal with the goal of delineating pathogenesis of glomerulonephritis. The
ultimate goal of this line of research is to develop genetic determinants of autoimmune-mediated renal
diseases may lead to identification of biomarkers for early detection, intervention and development of novel
treatments (NIDDK Strategic Research Plans for Genetics and Biological Factors).

## Key facts

- **NIH application ID:** 9925778
- **Project number:** 5K01DK119549-02
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Youngji Na
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $151,610
- **Award type:** 5
- **Project period:** 2019-05-06 → 2020-11-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9925778

## Citation

> US National Institutes of Health, RePORTER application 9925778, Rare variant analysis of glomerulonephritis (5K01DK119549-02). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/9925778. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*