# Genetic and genomic approaches to better understand the clinical heterogeneity in inflammatory bowel diseases

> **NIH NIH U01** · CEDARS-SINAI MEDICAL CENTER · 2021 · $447,457

## Abstract

The inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC), are
significant causes of morbidity with recent estimates suggesting there are more than 3 million
Americans with IBD with very significant financial burden to the US economy. More than 200
genetic loci that increase susceptibility to IBD have been identified with the anticipation that an
understanding of the molecular architecture of IBD will lead to improved outcomes for patients.
However, there are significant challenges remaining to achieve this and this proposal seeks to
address some of these key issues. 1) The majority of advances have been made in European
ancestry populations and we aim to continue our efforts to recruit and study non European
populations to extend the benefits of these advances to all parts of society. 2) We will address
unmet medical needs by focusing on genetic discovery in two areas: peri anal fistulizing CD is
associated with poor quality of life, significant morbidity, and poor response to treatment; and
non response to anti TNF therapy which happens in the majority of subjects with IBD. This
latter phenotype is increasingly important to define as new therapeutic options become
available for treating IBD. 3) Many of the IBD associated loci fall in intergenic ('junk' DNA)
regions and their functional consequences remain unclear. Using innovative genomic
approaches together with state of the art bioinformatics strategies we propose to identify the
processes that are influenced by the susceptibility loci we have identified. 4) And finally we will
extend our previous observations that Paneth cell phenotypes are an important readout of
gene environment interactions, as well as an important clinical biomarker, in CD to populations
from a variety of ethnicities and geographical locations. Collectively, these approaches will shed
additional insights into the underlying causes of IBD as well as identify additional biomarkers for
use in clinical practice and highlight novel potential therapeutic pathways for IBD.

## Key facts

- **NIH application ID:** 10238132
- **Project number:** 5U01DK062413-20
- **Recipient organization:** CEDARS-SINAI MEDICAL CENTER
- **Principal Investigator:** Dermot Patrick McGovern
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $447,457
- **Award type:** 5
- **Project period:** 2002-09-30 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10238132

## Citation

> US National Institutes of Health, RePORTER application 10238132, Genetic and genomic approaches to better understand the clinical heterogeneity in inflammatory bowel diseases (5U01DK062413-20). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10238132. Licensed CC0.

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