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NIDDK HERITAGE: Harnessing Tandem Repeats in Multi-Ancestry Metabolic Gene-Phenotype Relationships

Award Number: RC2DK144739
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: 07/15/2026
PERIOD OF PERFORMANCE END DATE: 03/31/2031

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NIDDK HERITAGE: Harnessing Tandem Repeats in Multi-Ancestry Metabolic Gene-Phenotype Relationships - PROJECT SUMMARY Diabetes and obesity are two of the most prevalent and fastest growing metabolic disorders. Both are heavily influenced by genetic factors, with heritability estimates reaching up to 80%. Genome-Wide Association Studies (GWAS) and target sequencing efforts have identified thousands of single nucleotide polymorphisms (SNPs), including rare variants, but these collectively account for a small fraction of the heritability. Thus, a significant portion of the genetic influence on diabetes and obesity remains unexplained, hindering efforts to develop effective prevention and treatment strategies. Furthermore, metabolic traits and their complications vary by ancestral background, yet we have limited understanding of the genetic contributors to the heterogeneity of diabetes and obesity. Capitalizing on research investments and unique expertise, our group has unraveled a new code in metabolic gene-phenotype relationships. We found that variation in number of DNA tandem repeats (e.g., 10 vs. 15 CAG repeats) is a significant contributor to genetic heterogeneity and underlies many previously unrecognized diseases, including complex polygenic traits. Aligned with the mission of NIH and the goals of the RC2 mechanism, we founded the HERITAGE study to develop tandem repeat (TR) resources that will enhance our understanding of the genetic architecture of diabetes and obesity. In Aim 1, we leverage existing whole-genome sequencing (WGS) data from diabetes and obesity cohorts to establish a TR atlas and perform TR-GWAS to identify new genetic contributors. Aim 2, focuses on using innovative computational tools to reveal the molecular mechanisms through which TRs impact diabetes and obesity and validate causal effects of TRs. By combining expertise in basic metabolic biology, bioinformatics, and population genetics, our team will develop a comprehensive TR resource to advance knowledge of the genetics of diabetes and obesity.


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 = $1,581,254 )
2026	2026	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	7/16/2026	NEW	$1,581,254
														Subtotal = $1,581,254

Grand Total All Awards = $1,581,254

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NIDDK HERITAGE: Harnessing Tandem Repeats in Multi-Ancestry Metabolic Gene-Phenotype Relationships

Award Number: RC2DK144739

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: 07/15/2026

PERIOD OF PERFORMANCE END DATE: 03/31/2031

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