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

Award Number: R01DK138367
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/01/2024
PERIOD OF PERFORMANCE END DATE: 01/31/2027

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


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $1,402,745 )
2026	2026	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	1/26/2026	NON-COMPETING CONTINUATION	$1,402,745
														Subtotal = $1,402,745

Issue Date FY: 2025 ( Subtotal = $1,547,165 )
2025	2025	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	4/2/2025	NON-COMPETING CONTINUATION	$1,547,165
														Subtotal = $1,547,165

Issue Date FY: 2024 ( Subtotal = $1,467,161 )
2024	2024	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	1/31/2024	NEW	$1,467,161
														Subtotal = $1,467,161

Grand Total All Awards = $4,417,071

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

Award Number: R01DK138367

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 02/01/2024

PERIOD OF PERFORMANCE END DATE: 01/31/2027

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