# Identifying population-specific IBD-associated mutations, genes and pathways

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2021 · $339,000

## Abstract

SUMMARY
Inflammatory bowel disease (IBD) is a group of disorders that involve chronic inflammation of the colon and
small intestine. The two major types of IBD are ulcerative colitis (UC): long term inflammation and ulcers of the
colon and rectum, and Crohn’s Disease (CD): inflammation of the digestive tract lining that can spread into
affected tissues. IBD can be debilitating, and life threatening in severe cases. There are currently over 1.5 million
estimated IBD patients in the United Stated. IBD results in substantial direct healthcare costs (over US$6 billion
per year in the United States) and the incidence of IBD continues to rise worldwide. Over the last two decades
genetics has been shown to be a major contributor to IBD predisposition. Most studies investigating IBD have
focused on genome-wide association studies (GWAS) of common genetic variants, mostly in European
populations. While it has been shown that IBD has a substantial Mendelian/monogenic component of high impact
mutations, and that it is likely that a significant proportion of IBD mutations and genes are population-specific
(for example: occur in African Americans and not in Europeans), there has not yet been an effort to perform in
IBD (or in any other disease) a large-scale investigation of population-specific IBD-causing high-impact
mutations, genes and pathways. Understanding population-specific IBD genomics would ultimately contribute to
personalized medicine of IBD patients, where the population background of the patient will be crossed with the
patient’s estimated IBD mutations to tailor an optimal therapy.
We hypothesize that IBD has a major component of population-specific high-impact predisposing mutations and
genes, and that these mutations and genes can be discovered with gene burden analyses on whole exome
sequencing (WES) data of IBD patients. We therefore propose to perform an ancillary study on IBDGC’s WES
data of IBD patients that consists of four major human populations: Ashkenazi Jewish, African Americans,
Hispanics and Europeans. IBDGC is ideal for such a study, as it contains enough samples per population group
to perform WES gene burden analyses of high-impact genetic variants (shown in preliminary results). We also
have full access to Mount Sinai’s BioMe BioBank, which contains WES data of over 30,845 patients across
diverse populations (the majority being the four populations of IBDGC) including IBD patients, that will boost
our sample sizes and analysis power. We propose a rigorous analysis pipeline combining state-of-the-art
established software with cutting-edge approaches across human population and disease genomics, as well as
diverse computational algorithms to: (1) obtain a high-quality set of IBD cases and controls by genetic population
estimates of Ashkenazi Jewish, African Americans, Hispanics and Europeans on IBDGC data; (2) performing a
gene burden cases-controls analysis for high impact variants in each population; and (3) identifying popul...

## Key facts

- **NIH application ID:** 10180961
- **Project number:** 5R01DK123530-03
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Yuval Itan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $339,000
- **Award type:** 5
- **Project period:** 2019-09-20 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10180961

## Citation

> US National Institutes of Health, RePORTER application 10180961, Identifying population-specific IBD-associated mutations, genes and pathways (5R01DK123530-03). Retrieved via AI Analytics 2026-06-02 from https://api.ai-analytics.org/grant/nih/10180961. Licensed CC0.

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