# Multi-omic studies of asthma severity in an African ancestry population

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2020 · $687,623

## Abstract

Asthma disproportionately affects underrepresented minorities, and is a complex disease where the interplay
between genetic factors and environmental exposures controls susceptibility. Airway epithelial cells are critical
in the development of allergic airway inflammation, represent the first line of defense against environmental
stimuli, and the nasal airway epithelium has been shown to mirror the bronchial epithelium morphologically and
functionally. Genome-wide association studies (GWAS) have been successful in identifying genes associated
with increased risk of asthma, but there is a substantial gap between single nucleotide polymorphism (SNP)
associations discovered by GWAS and understanding how these loci control disease. Because nearly all of
the asthma GWAS associations to date involve SNPs in intergenic or intronic regions, it seems likely that
polymorphism markers in regulatory elements may account for a large portion of the missing heritability. It is
also increasingly clear that epigenetic mechanisms may be causal for asthma, and studies suggest that SNPs
are likely to affect both gene expression and methylation independently of one another; thus, both
transcriptome and methylation data can independently be informative for defining functional genes. We
recently completed whole genome sequencing (WGS) on 1,100 African Caribbean asthmatics and non-
asthmatics, extensively phenotyped and followed participants for >20 years, living in a homogeneous, well-
characterized environment, comprising the Barbados Asthma Genetics Study. Currently a subset is being
recruited as part of the NIH-supported parent grant to characterize the transcriptome of peripheral blood CD4+
T cells, and perform an expression Quantitative Trait Locus (eQTL) study combining WGS and transcriptomic
data. To test the hypothesis that genetic determinants confer risk to asthma, and expressed variation in the
transcriptome and methylome of the nasal epithelium may mediate the relationship between genotype,
phenotype and environment, we propose to integrate one of the most comprehensive WGS databases on an
African ancestry population with next-generation sequencing technology (RNA-Seq) and eQTL mapping to
elucidate how genetic variation controls differ in quantitative levels of gene expression of nasal airway
epithelial cells. The specific aims of this application build upon the infrastructure of an ongoing program, and
include the following: (i) identify cis- and trans-effects of variants identified in the transcriptome for isolated
nasal epithelial cells from atopic asthmatics; (ii) identify eQTL patterns from nasal epithelial cells specific to
atopic asthma; and (iii) identify DNA methylation changes associated with atopic asthma in the nasal airway
epithelium, followed by an unbiased QTL analyses on the methylome (meQTL) and integrating novel eQTLs
and meQTLs from transcript expression and methylation, respectively, to determine whether these QTLs
identified in airway e...

## Key facts

- **NIH application ID:** 9851798
- **Project number:** 5R01AI132476-03
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Kathleen C Barnes
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $687,623
- **Award type:** 5
- **Project period:** 2018-02-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9851798

## Citation

> US National Institutes of Health, RePORTER application 9851798, Multi-omic studies of asthma severity in an African ancestry population (5R01AI132476-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9851798. Licensed CC0.

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