# Characterizing individual- and subtype-specific risk factors and treatments in asthma

> **NIH NIH K25** · UNIVERSITY OF CHICAGO · 2021 · $173,016

## Abstract

Project Summary/Abstract
Asthma is a chronic respiratory disease affecting about 340 million people worldwide, yet its causal biology,
environmental risks, key cell types, and optimal treatments remain under-characterized. This difficulty is partly
due to clinical heterogeneity, as different risk factors drive asthma for different people. Asthma subtype studies
have already begun to reveal important aspects of this heterogeneity. However, asthma subtypes remain
nascent and ambiguous and have not yet realized their potential utility for scientific studies and precision
treatments. In particular, genetics has not been fully exploited for asthma subtyping, though it has a unique
ability to assess the causal biological significance of subtypes and can identify key cell types; conversely, prior
subtyping studies are susceptible to coincidental subtypes that are not directly relevant to asthma biology.
Furthermore, prior studies have used basic methods which are liable to bias and low power. To address these
limitations, we will develop a powerful and robust framework to pinpoint and genetically characterize
asthma subtypes, and we will broadly apply it in large, deeply phenotyped, and diverse cohorts. Our study
will identify novel subtypes and their demographic, genomic, cellular, and clinical etiologies, which can suggest
precision treatments and improve power and interpretation in basic and translational research. Our work will
improve genetic prediction of asthma, particularly in understudied populations. Finally, our approach and
freely released methods will provide a broad template for complex trait subtyping.
To accomplish these goals, we will study four large biobanks, which offer unprecedented sample size, clinical
depth, and demographic diversity. We will use functional genomics to link genetic heterogeneity to causal
and cell type-specific molecular mechanisms. We will build on our prior machine learning tools to
identify subtypes, quantify their genetic and clinical significance, and infer their dominant cell types. Our
methods are unique by correcting for confounding population structure, which is crucial for genetic subtyping:
spurious genetic associations led prior studies to propose severely biased and regressive nosology.
A key goal of this proposal is the PI’s retraining in asthma biology, pulmonology, and functional genomics. This
will be achieved by close mentorship from Professors Carole Ober, Julian Solway, Yoav Gilad, and Matthew
Stephens, as well as didactic courses in the UChicago Department of Medicine and Institute for Translational
Medicine. This retraining will maximize the biomedical impact of our study by enabling the PI to deeply connect
quantitative results to core facets of asthma pathology and will establish the PI as an independent asthma
researcher who can optimally apply his statistics and machine learning background to tackle essential
biomedical hurdles.

## Key facts

- **NIH application ID:** 10191398
- **Project number:** 1K25HL157603-01
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** Andrew Dahl
- **Activity code:** K25 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $173,016
- **Award type:** 1
- **Project period:** 2021-08-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10191398

## Citation

> US National Institutes of Health, RePORTER application 10191398, Characterizing individual- and subtype-specific risk factors and treatments in asthma (1K25HL157603-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10191398. Licensed CC0.

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