# Childhood Asthma in Urban Settings Leadership Center Administrative Supplement for Genotyping Yr4

> **NIH NIH UM1** · UNIVERSITY OF WISCONSIN-MADISON · 2024 · $399,594

## Abstract

Contributions of Genetics and DNAm to Phenotypes, Severity & Treatment Response in Urban Children
Aim 1. To utilize the novel Asthma&Allergy Array to identify DNAm patterns in blood that link genetics and
environmental exposures to the expression of asthma phenotypes in urban children in the APIC study.
Rationale: Epigenetic analyses provide a critical link between genetics and environmental exposures in the
expression of disease. DNAm is the most common epigenetic mark and methylation levels at CpG sites are
influenced by exposures (environment), genetic variation, or both. Importantly, DNAm can mediate the effects of
both genetic and environmental risk factors on health outcomes. Carole Ober and colleagues developed the novel
Asthma&Allergy array through a study of nasal epithelium from URECA and Childhood Origins of Asthma (COAST)
birth cohort participants. Assessment of DNAm in blood, nasal brush, and sputum samples from the Asthma
Phenotypes in the Inner City (APIC) study holds great potential to identify potential mechanisms by which various
environmental exposures (microbial, allergens, pollutants, etc) contribute to the expression of various respiratory
phenotypes such as difficult vs. easy to control asthma and the APIC phenotypes described by Zoratti et al. This
provides a unique opportunity to explore how epigenetic patterns are differentially related to asthma phenotypes
(such as the T2-low cluster B). By including the nasal and sputum samples, which are available for a subset of the
population, we can compare and contrast these relationships across compartments (blood, upper and lower airway).
Preliminary Data: Using an empirical Bayes approach to factor analysis and the Asthma&Allergy DNAm array, we
recently defined in children three factors comprised of between 6,188 and 659 CpGs from nasal brush samples that
are associated with allergic phenotypes in URECA. The genes that are correlated with these DNAm-defined factors
are significantly enriched in networks downstream of IFNG and IRF9 (factor 5), SEPTIN1 and BBS1 (factor 9), and
TSLP, IL4, IL13, and STAT3 (factor 16). Based on the direction of gene effects in these networks, the factor 5 genes
suggest “impaired microbial response”, the factor 8 genes suggest “impaired barrier function”, and the factor 16
genes suggest “activated T2 immune response”.
Study Design: In this study, we propose to use the Asthma&Allergy array to analyze DNAm in blood samples from
more than 500 APIC children. Additionally, we will analyze DNAm in sputum and nasal brush samples from a subset
of these children. We will then assess patterns of DNAm and their association to asthma phenotypes and severity,
as well as environmental exposures assessed in APIC. Further, we can integrate this data with the whole genome
sequencing previously performed to assess meQTLs and understand the role of genetic variation in DNAm patterns.
Anticipated Results & Interpretation: We anticipate that we will identify DNAm pattern...

## Key facts

- **NIH application ID:** 11091920
- **Project number:** 3UM1AI160040-04S1
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** James E. Gern
- **Activity code:** UM1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $399,594
- **Award type:** 3
- **Project period:** 2021-04-12 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11091920

## Citation

> US National Institutes of Health, RePORTER application 11091920, Childhood Asthma in Urban Settings Leadership Center Administrative Supplement for Genotyping Yr4 (3UM1AI160040-04S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11091920. Licensed CC0.

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