# Gene Discovery in Asthma and Allergic Diseases

> **NIH NIH U19** · UNIVERSITY OF CHICAGO · 2021 · $334,431

## Abstract

SUMMARY
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 account for an overall small
fraction of the genetic risk. Moreover, remarkably few of the GWAS findings 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 and omic tools for bridging the trajectory from GWAS to gene
discovery. Project 1 is a computational project in which we propose to systematically dissect the genetic
architecture of asthma and allergic diseases using a robust and comprehensive strategy for identifying candidate
causal variants and their target genes at asthma- and allergic disease-associated loci and characterizing their
phenotypic effects. We will utilize both existing data and those generated in the (Epi)Genomics Core and Project
2. The results of Project 1 will inform the selection of variants and genes for further studies in lung immune cells
in Project 2 and for selection of genomic regions for enhancer assays and variants for functional studies in the
(Epi)Genomics Core. We will achieve our goals through three aims. In Aim 1, we will use functional annotations
in asthma- and allergic disease-relevant cell types, including airway epithelial cells, airway smooth muscle and
lung immune cells, as well as peripheral immune cells, all in resting and activated states, to partition the
heritability at asthma and allergic diseases GWAS loci and assign cell type/state for associated variants and loci.
In Aim 2, we will use information from Aim 1 to perform fine mapping at asthma and allergic disease GWAS loci
using two complementary Bayesian approaches to identify putatively causal SNPs and their target genes. In
Aim 3, we will characterize the downstream phenotypic effects of causal variants on both broad categories of
disease groups in the UK Biobank and on specific asthma and allergic disease mechanistic subtypes, or
endotypes, in deeply phenotyped ethnically-diverse subjects in asthma birth cohorts. These studies will provide
novel information on the dominant cell type(s) contributing to asthma and allergic disease endotypes and
comorbidities, as well as on shared mechanisms between asthma and allergic diseases, and potentially with
other traits discovered in Aim 3. Achieving these goals will ultimately identify causal SNPs and causal genes at
most AAD loci and the primary cell type(s) in which they exert their effects on phenotypes and endotypes of
asthma and allergic...

## Key facts

- **NIH application ID:** 10261990
- **Project number:** 1U19AI162310-01
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** Carole Ober
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $334,431
- **Award type:** 1
- **Project period:** 2021-07-19 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10261990

## Citation

> US National Institutes of Health, RePORTER application 10261990, Gene Discovery in Asthma and Allergic Diseases (1U19AI162310-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10261990. Licensed CC0.

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