# Integrative multi-omics for discovery of molecular pathways associated with diabetic retinopathy

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2024 · $782,235

## Abstract

PROJECT SUMMARY
One of the areas of emphasis on the NEI strategic plan is to bridge the gap between genomics and mechanisms
of disease. Diabetic retinopathy (DR) is a leading cause of blindness and disproportionately affects Hispanics/
Latinos (HL). DR-specific blood biomarkers and systemic treatments are not used clinically. Although research
into biomarkers and genetic variants has informed our understanding of DR, whether these signatures cause or
are caused by DR, and how genetic variants contribute to DR etiology is still not clear. Further, few of these
studies have meaningful representations of HL despite their high DR burden. Because transcript and metabolite
levels provide a window into gene function, they can help us interpret genome-wide association study (GWAS)
results to better understand complex diseases like DR. Given the growing HL population in the US and their
disproportionate cardiometabolic disease burden, HL representation in functional genomic studies of diabetic
sequelae is imperative. The Cameron County Hispanic Cohort (CCHC) is a cohort of HL with poor
cardiometabolic health and high risk for DR. Participants range between metabolically healthy and metabolically
disordered individuals without or with diabetes, some with various levels of DR. We will quantify differential
transcript (Aim 1) and metabolite (Aim 2) abundance between participants with Type 2 diabetes (T2D) with or
without clinical diagnosis of DR in CCHC and replicate our findings in the Hispanic Community Heath
Study/Study of Latinos (HCHS/ SOL), an independent, extant, diverse, larger HL dataset with T2D and self-
reported DR status. Using gene regulatory and metabolite network and pathway analyses we will clarify DR
pathophysiology, inform novel blood biomarkers and drug targets for DR, and validate their temporal precedence
with DR using both cohorts. In Aim 3, we will apply two-sample Mendelian randomization and colocalization
methods to interpret known and novel transcriptomic and metabolomic biomarkers (eQTLs and mQTLs) using
results from a novel HL-specific GWAS meta-analysis and the literature. Finally, using diverse electronic health
record (EHR)-linked databases, we will perform eQTL-, mQTL-, variant-, and polygenic risk score-based
phenome wide association and enrichment studies to expand our understanding of the broader clinical comorbid
profile of, and pathogenic mechanisms shared with, DR. Our study will clarify mechanistic causes/consequences
of DR-associated expression patterns in the blood. The aims will independently inform novel diagnostic and
therapeutic systemic DR-targets and our understanding of the causality and broader clinical implications of blood
signatures dysregulated in DR. This project meets several NIH/NEI strategic goals including: 1) enhancing our
understanding of ocular epidemiology in groups under-represented in vision science; 2) enriching data capturing
molecular signatures of disease; 3) using data science to integrate...

## Key facts

- **NIH application ID:** 11000008
- **Project number:** 1R01EY036258-01A1
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Jennifer Below
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $782,235
- **Award type:** 1
- **Project period:** 2024-09-01 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11000008

## Citation

> US National Institutes of Health, RePORTER application 11000008, Integrative multi-omics for discovery of molecular pathways associated with diabetic retinopathy (1R01EY036258-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11000008. Licensed CC0.

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