# Identifying cell-type specific genetic control of T1D risk variants in TEDDY

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 2024 · $1,467,161

## Abstract

Type 1 diabetes (T1D) is a complex disorder that arises from the action of multiple genetic and
environmental risk factors with population cumulative risk approaching 1 in 300 children. The
disease process for T1D consists of initiation of an immune attack targeted to insulin secreting
beta cells in the islets, modifying, impairing, and (ultimately) destroying the beta cells. Genome-
wide association studies (GWAS), performed by ourselves and others, identified more than 100
chromosomal loci where there is significant, replicated evidence of association with T1D. As
shown by us in the Type 1 Diabetes Genetic Consortium ImmunoChip fine-mapping analysis,
and other studies, ~ 98-99% of T1D credible set of SNPs are in the non-coding region of the
genome and preferentially map in enhancer regions active in immune cells. The proposed study
is an ancillary research project of the Environmental Determinants of Diabetes in the Young
(TEDDY) study. TEDDY was designed to discover environmental triggers of T1D in a
prospective cohort of newborns at genetic risk, followed multiple times per year with collection of
samples for deep phenotypic and biomarker profiling. This project will utilize longitudinal
samples and their rich demographic, genetic, and immune markers collected on TEDDY
participants. We will use single-cell sequencing technology to monitor immune markers at the
protein and transcription levels to generate profiles for different stages of islet autoimmunity. To
gain a comprehensive understanding of the T1D risk genes that function in initiation and
progression of islet autoimmunity, we propose to apply single-cell sequencing to map T1D risk
variants that alter gene expression in circulating immune cells; we will use immune cell-surface
markers for cell type identification and examine immune profiles at initiation and progression to
T1D. To identify biological pathways, that T1D genes function in, we will construct a reference
co-expression network and refine predicted gene-gene interactions with Bayesian networks.

## Key facts

- **NIH application ID:** 10797290
- **Project number:** 1R01DK138367-01
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Suna Onengut
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,467,161
- **Award type:** 1
- **Project period:** 2024-02-01 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10797290

## Citation

> US National Institutes of Health, RePORTER application 10797290, Identifying cell-type specific genetic control of T1D risk variants in TEDDY (1R01DK138367-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10797290. Licensed CC0.

---

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