# Prioritizing and Characterizing T Cell-Relevant Genetic Variants Associated with Autoimmune Diseases

> **NIH NIH K22** · BENAROYA RESEARCH INST AT VIRGINIA MASON · 2022 · $108,000

## Abstract

PROJECT SUMMARY
Greater than 8% of the United States population suffers from autoimmune disease, but, due to complex non-
Mendelian inheritance, the genetic determinants of autoimmune disease are difficult to parse. To begin to
address this problem, genome-wide association studies (GWAS) have identified thousands of genetic variants
that track with disease, allowing the field of autoimmunity to focus on key disease-causal regions of the
genome. However, the exact causal genetic variants for most of these associations remain unidentified, and
thus the genes and pathways they alter remain poorly understood. To tackle this problem, I first will enrich for
likely causal variants for diseases in which T cells are known to be pathogenic, including multiple sclerosis,
type I diabetes, rheumatoid arthritis, psoriasis, and inflammatory bowel disease. I will use a high-throughput
approach to test 20,000 variants for allelic skew in reporter expression. Furthermore, for 4 highly important
GWAS loci (each with more than 10 disease associations), I will screen for regulatory regions that alter gene
expression and the disease-associated variants that lie within these regions. With these two approaches (and
other genomic data, such as chromatin accessibility and allele-specific transcription factor ChIP-seq), I will
prioritize variants for engineering in the genomes of primary cells, and determine the effects of these
engineered alleles on expression, activation, and polarization of T cells. This project will result in exhaustive
characterization of variants associated to 5 important autoimmune diseases, elucidation of the regulatory
architecture of 4 highly important disease loci, and experimental validation of 10 putatively causal variants
through editing them into the genome of primary T cells. This work will provide an extensive resource for
GWAS follow-up studies, help bring the field closer to understanding the pathways and regulatory architecture
involved in disease, and inform approaches for identifying new targeted therapeutics for autoimmunity.

## Key facts

- **NIH application ID:** 10320334
- **Project number:** 5K22AI153648-02
- **Recipient organization:** BENAROYA RESEARCH INST AT VIRGINIA MASON
- **Principal Investigator:** John Philip Ray
- **Activity code:** K22 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $108,000
- **Award type:** 5
- **Project period:** 2020-12-18 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10320334

## Citation

> US National Institutes of Health, RePORTER application 10320334, Prioritizing and Characterizing T Cell-Relevant Genetic Variants Associated with Autoimmune Diseases (5K22AI153648-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10320334. Licensed CC0.

---

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