# Integrated genetic, omic, and immunologic studies to identify endotypes and novel drug targets for asthma and allergic diseases

> **NIH NIH U19** · UNIVERSITY OF CHICAGO · 2024 · $292,167

## Abstract

ABSTRACT
Asthma and allergic diseases are among the most common chronic diseases in children and adults, costing
our health care system over $80 billion per year. Rates have been increasing over the past 40 years and
therapeutic advances have been incremental. Over 150 loci have been reported in large genome-wide
association studies (GWAS) of asthma and allergic diseases, but their individual effects are small and these
variants account a small fraction of the overall genetic risk. Moreover, remarkably few of the GWAS findings for
asthma and allergic diseases have led to discoveries of causal variants or causal genes that contribute to
asthma and allergic disease pathogenesis. The latter has been particularly challenging due in part to the
significant clinical heterogeneity of these diseases, and in part to the lag in the development of powerful
statistical, molecular, and immunologic tools for bridging the trajectory from GWAS to gene discovery to
biology to translation. In this application, we propose a robust and comprehensive strategy for identifying
candidate causal variants and their target genes at asthma and allergic disease-associated loci, and for
characterizing (i) their functional effects in asthma and allergic disease-relevant cells types, including bronchial
epithelial cells, airway smooth muscle and lung immune cells, as well as peripheral immune cells, all in resting
and activated states; (ii) their downstream phenotypic effects on both broad categories of disease groups and
traits in the UK Biobank resource and on specific asthma and allergic disease endotypes in deeply phenotyped
ethnically-diverse subjects participating in asthma birth cohorts; and (iii) their immunologic effects in resting
and activated lung lymphocytes and myeloid cells and in “humanized locus” BAC-engineered mouse models.
These goals will be accomplished through a highly collaborative and synergistic program that includes two
projects, a service core, and an administrative core that together will that bridge the trajectory from GWAS to
translation through highly integrated studies by an exceptional team of investigators with expertise in genetics,
(epi)genomics, statistical genetics, and immunology. Achieving these goals will ultimately identify novel drug
targets and the individuals most likely to respond, providing a framework for precision medicine and
personalized treatment of asthma and allergic diseases.

## Key facts

- **NIH application ID:** 11137450
- **Project number:** 3U19AI162310-04S1
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** Marcelo A. Nobrega
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $292,167
- **Award type:** 3
- **Project period:** 2021-07-19 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11137450

## Citation

> US National Institutes of Health, RePORTER application 11137450, Integrated genetic, omic, and immunologic studies to identify endotypes and novel drug targets for asthma and allergic diseases (3U19AI162310-04S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/11137450. Licensed CC0.

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