# Identifying novel osteoarthritis risk genes using GWAS, chondrocyte genomics, and genome editing

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2022 · $508,492

## Abstract

Project Abstract
Despite the high global prevalence of knee osteoarthritis (OA), treatment options have been limited to symptom
management and total joint replacement in large part because the mechanisms driving knee OA remain poorly
understood. Genome-wide association studies (GWAS) suggest that non-coding genetic variation is a major
contributor to knee OA disease-risk; however, the LD structure of human genomes, the long-range nature of
transcriptional regulation, and the lack of genome-editable and biologically accurate systems in which to study
OA have created a bottleneck that hinders our ability to translate GWAS findings into new treatments. The
overall objective of this proposal is to identify putative causal knee OA risk variants, map them to their target
genes, and quantify their phenotypic impact in chondrocytes. We will identify regulatory regions activated
in response to cartilage degradation (Aim 1), map regulatory loci and GWAS variants to their target genes
(Aim 2), and quantify the phenotypic impacts of knee OA-associated variants using an ex vivo model of the
chondrocyte OA phenotype (Aim 3). This work will break down existing barriers in knee OA genetics, improve
our mechanistic understanding of knee OA, and provide new risk genes for further study and therapeutic
development.

## Key facts

- **NIH application ID:** 10445527
- **Project number:** 1R01AR079538-01A1
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** RICHARD F LOESER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $508,492
- **Award type:** 1
- **Project period:** 2022-09-20 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10445527

## Citation

> US National Institutes of Health, RePORTER application 10445527, Identifying novel osteoarthritis risk genes using GWAS, chondrocyte genomics, and genome editing (1R01AR079538-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10445527. Licensed CC0.

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