# Integrative multi-omic risk assessment at diagnosis and during disease progression in African-Americans with Inflammatory bowel disease

> **NIH NIH U01** · EMORY UNIVERSITY · 2023 · $573,949

## Abstract

Summary
Inflammatory bowel disease (IBD) in African Americans (AA) is likely to progress towards
complicated disease and debilitating outcomes. These outcomes are likely rooted in genetic,
epigenetic, microbial, and metabolic factors. We have made substantial advances in this research
area, and over the past two funding cycles as Ancillary contributors to the IBD-GC produced
sufficient outcomes to drive new studies, and here propose a focused set of three aims building
on those advances. (1) Differences in allele frequency and effect size substantially impact
polygenic risk assessment, (2) Gene expression in the ileum of AA IBD patients tends to display
significant up-regulation of markers associated with adverse disease progression, including TNF
response. (3) Genomic DNA methylation patterns in the rectum of IBD patients is maintained,
reflecting the dominance of epithelial contributions over transient inflammatory signatures from
the immune compartment. (4) AA tend to have a reduced mucosal fibroblast component relative
to European cases. (5) Polygenic risk scores (PRS) for IBD are substantially modified by diet,
smoking and alcohol consumption, but these factors have not been evaluated in AA despite
substantial cultural differences. (6) IBD is associated with changes in the gut microbiome and
differs by ethnicity and urban/rural lifestyle, suggesting a butyrate-induced modulation of epithelial
and immune function. (7) We can experimentally evaluate the impact of genetic and metabolic
perturbations on cellular function using patient biopsy derived organoids. Taken together, these
insights have led to the overarching hypothesis that environmental factors modulate the
epigenome and microbiome, driving adverse health disparity in AA with IBD. To test this, we
propose the following three Specific Aims. For Aim 1, we will define the genetic architecture of
IBD in AA by expanding the IBD-GC sampling, developing an inception cohort, and evaluating
PRS×Environment interactions. In Aim 2, we will test the hypothesis that a subset of ileo-colonic
methylation signatures are consistent with a role in IBD onset and/or severity, rather than an
outcome of IBD, and determine whether these signatures are independent of, or interacting with,
the environmental factors of Aim 1. Finally, in Aim 3, we will use ileo-colonic biopsies and enteroid
cultures to test the hypothesis that differences in the microbiome drive metabolic profiles that
associate with gut dysbiosis in IBD. Together, our multi-omic approach and breadth of expertise
across multiple disciplines will shed new light on disease outcomes of IBD related to differences
in the genomics and metabolomics of AA ancestries.

## Key facts

- **NIH application ID:** 10707294
- **Project number:** 5U01DK134191-02
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** SUBRA KUGATHASAN
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $573,949
- **Award type:** 5
- **Project period:** 2022-09-30 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10707294

## Citation

> US National Institutes of Health, RePORTER application 10707294, Integrative multi-omic risk assessment at diagnosis and during disease progression in African-Americans with Inflammatory bowel disease (5U01DK134191-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10707294. Licensed CC0.

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