# Understanding genetic architecture and host-microbiome interactions in Inflammatory bowel disease in under-represented minority populations and in patients with unmet medical need.

> **NIH NIH U01** · CEDARS-SINAI MEDICAL CENTER · 2024 · $546,312

## Abstract

Background: The inflammatory bowel diseases (IBD) are a chronic inflammatory disease of the gastrointestinal
tract that are associated with a poor quality of life. There is no cure for IBD, and most people require lifelong
immunosuppressive medication and also frequently need surgery. The cause of Crohn’s disease (CD) and
ulcerative colitis (UC), the two most common forms of IBD, are unknown but it is widely accepted that they
develop in genetically susceptible individuals in response to environmental factors for which the most compelling
evidence is the microbiome. Traditionally regarded as diseases of Northern European (EUA) and Ashkenazi
Jewish ancestry the prevalence of IBD is rapidly rising in minority populations such as Hispanic and African
American populations who have been under-represented in research. The objectives of our study include: the
delineation of the genetic architecture of IBD in Hispanics populations; describe the gene-microbiome
interactions in Hispanics; an understanding of the underlying molecular causes of lack of response to the most
widely used biologic therapies in IBD; and importantly, work that will determine some of the functional effects
of these genetic variants. We will achieve these objectives by addressing the following specific aims. In aim 1
we will decipher genetic architecture of IBD and investigate host-microbiome interactions using a biomarker-
based inference approach. In aim 2 we will use advanced technology investigating gene and protein expression
in individual cells in the lining of the gut to identify signatures associated with response to medication. In aim 3
we will use human intestinal epithelial cell culture systems to screen for function of new IBD susceptibility genes.
Research Design: in collaboration we will build the largest collection of IBD subjects of Hispanic ancestry and
use state of the art genetic approaches to identify genetic signals associated with development of IBD. We
anticipate that some of these signals will overlap with those we’ve observed in EUA subjects and others will be
unique to the Hispanic population. Since there is significant admixture of Native American ancestry in the North
American population, we anticipate that we will also identify some genetic signals that are ‘peculiar’ to Native
Americans. There have been few studies investigating host-microbiome interactions in Non-EUA populations
and we will address this by investigation serum markers that are surrogates for the microbiome thereby allowing
us, for the first time, to investigate interactions between genetic variation and the microbiome in Hispanic
populations. In parallel we will look at gene expression signatures in biopsies from the gut to determine the
molecular signature that underlies a very important clinical issue of non-response to our most effective
medications. Finally, we use model systems to determine the functional consequences of the genetic variants
that we have identified. We will due thi...

## Key facts

- **NIH application ID:** 10909896
- **Project number:** 5U01DK062413-23
- **Recipient organization:** CEDARS-SINAI MEDICAL CENTER
- **Principal Investigator:** Dermot Patrick McGovern
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $546,312
- **Award type:** 5
- **Project period:** 2022-09-30 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10909896

## Citation

> US National Institutes of Health, RePORTER application 10909896, Understanding genetic architecture and host-microbiome interactions in Inflammatory bowel disease in under-represented minority populations and in patients with unmet medical need. (5U01DK062413-23). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10909896. Licensed CC0.

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