# Epigenome-wide association study of childhood asthma

> **NIH NIH R01** · LA JOLLA INSTITUTE FOR IMMUNOLOGY · 2020 · $790,887

## Abstract

PROJECT SUMMARY
In this multi-PI proposal we will investigate the role of epigenetic mechanisms in the development of asthma in
children. Asthma affects 1 in 15 Americans -- over 23 million people -- thus making it one of the country's most
common and also costly diseases. Among children, asthma is the third-ranking cause of all hospitalizations
and the leading cause of school absenteeism. Current therapies do not cure asthma, prompting us to adopt
“out-of-box” approaches to find novel preventive therapies for asthma. Numerous genome-wide association
studies (GWAS) have been instrumental in identifying common genetic variations that affect asthma
susceptibility. By contrast, despite overwhelming evidence of the role of environmental exposures during fetal
and early childhood in shaping disease outcomes, the systematic assessment of epigenetic variations has
lagged behind. Here, we will conduct the first longitudinal epigenome-wide association study (EWAS) to
identify epigenetic variations that are associated with asthma susceptibility in children.
The proposal will capitalize on two unique recently established longitudinal birth cohorts in the United Kingdom.
(i) The Immune Tolerance in Early Childhood (ITEC) is an observational cohort, which consists of 200 children
at high risk of developing asthma. (ii) The Mite Allergen Prevention Study (MAPS, n=111) is a primary
prevention randomized controlled trial in which house dust mite oral immunotherapy (OIT) was administered to
6-month-old infants at high risk of developing asthma. At 18 months, we found a significant reduction in allergic
sensitization in the OIT group and a trend towards reduced onset of wheeze and eczema.
We will test the hypothesis that asthma – a chronic allergic disease -- is characterized by perturbations in these
epigenetic processes in immune cells, that can be recognized and read out as long-range epigenetic changes
at relevant disease-associated loci. In Aim 1, we will identify `epigenetic variants' associated with the
susceptibility to asthma in children (n=200, ITEC cohort). Then, we will validate our discovery set of `epigenetic
variants' by performing a similar study in children from the MAPs cohorts (n=51, placebo arm); then, ask if
asthma-risk `epigenetic variants', common to children in ITEC and MAPS cohort, are erased by preventive
immunotherapy (n=53, treatment arm). In Aim 2, we will define the target genes of asthma-risk associated
`epigenetic variants' and verify if expression of target genes is affected by the presence or absence of
`epigenetic variants'; These studies will allow us to predict sets of novel “asthma-susceptibility genes” that are
likely to have an important role in the development of CD4 T cell driving asthma pathogenesis. We will then
test the function of these genes in primary human T cells using optimized micro-scaled immunological assays.
Overall, our discovery-based EWAS and follow up functional studies will identify novel genes and pathwa...

## Key facts

- **NIH application ID:** 9840861
- **Project number:** 5R01AI121426-04
- **Recipient organization:** LA JOLLA INSTITUTE FOR IMMUNOLOGY
- **Principal Investigator:** Syed HASAN Arshad
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $790,887
- **Award type:** 5
- **Project period:** 2017-01-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9840861

## Citation

> US National Institutes of Health, RePORTER application 9840861, Epigenome-wide association study of childhood asthma (5R01AI121426-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9840861. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*