# Gene discoveries in subjects with Crohn's disease of African descent

> **NIH NIH R01** · EMORY UNIVERSITY · 2020 · $737,396

## Abstract

ABSTRACT
Crohn’s disease (CD) is heritable. Most genetic discovery to date has been performed in
Caucasians of European descent. African Americans (AAs) endure a similar disease burden as
Caucasians, yet less than 1% of research, publications, or clinical trials have focused on AA
with CD. It remains to be seen whether these genetic markers will have prognostic utility in
admixed individuals, such as AAs. Furthermore, AAs are at higher risk for disease
complications and often have worse disease outcomes, suggesting that the underlying biology
of CD in AAs may be different than Caucasians. The genome of AAs is admixed (~80% West
African and 20% Caucasian), with greater diversity and shorter linkage disequilibrium (LD)
blocks. Higher levels of diversity can make genetic / post-GWAS studies more challenging, but
identifying causal variants in AA may prove easier because of shorter physical LD region. We
have successfully completed a well-powered GWAS for gene discoveries in AA. While common
susceptibility variants discovered in Caucasians are also generally found in AAs with IBD, new
AA-specific variants/loci in IBD, UC and human leukocyte antigen (HLA) region along with
several new regions of significant admixture linkage disequilibrium and multiple new signaling
pathways. Following these exciting results and discoveries, we propose a post GWAS studies
to comprehensively identify rare, causal and population specific variants in African Americans
with CD. Aim 1: We will double our AA cohort size by additional recruitment and fine map AA-
specific and common (to both Caucasians and AA) GWAS loci to test the hypothesis that
causal variants can be identified more easily due to shorter LD among AAs. Aim 2: Test the
hypothesis that expression quantitative trait loci (eQTL) and gene network analysis will identify
new AA-specific regulatory elements and causal loci / rare variants. Aim 3: Perform whole
genome sequencing (WGS) in AA cases for rare variant discovery. We propose that post
GWAS studies such as fine mapping, eQTL, and WGS in AA should be conducted in parallel to
Caucasians, to accelerate gene and pathway discovery in IBD. Proposed efforts will be jointly
undertaken with NIDDKGC utilizing their available resources.

## Key facts

- **NIH application ID:** 9982328
- **Project number:** 5R01DK087694-10
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** SUBRA KUGATHASAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $737,396
- **Award type:** 5
- **Project period:** 2011-03-01 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9982328

## Citation

> US National Institutes of Health, RePORTER application 9982328, Gene discoveries in subjects with Crohn's disease of African descent (5R01DK087694-10). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9982328. Licensed CC0.

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