# Integrative genomic, transcriptomic and proteomic studies of pulmonary function and COPD

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 2022 · $758,323

## Abstract

Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in the United States.
COPD is defined by a decrease in lung function as measured by pulmonary function testing (PFT), namely
forced expiratory volume in one second (FEV1) and its ratio to forced vital capacity (FEV1/FVC). While the main
risk factor for COPD is cigarette smoking, the risk of COPD also increases with age, and COPD can progress
despite smoking cessation. There are no current pharmacologic therapies that slow progression of COPD or
affect mortality. Large-scale genome-wide association studies (GWAS) of PFT and COPD have identified >
200 associated genetic loci. However, COPD and PFT GWAS have been limited by imperfect matching and
sample sizes of reference panels (e.g. HapMap or 1000 Genomes), and downstream interpretation has been
limited by lack of disease- and tissue-specific eQTL and pQTL resources and under-represention in African
American and Hispanic/Latino subjects for both common and rare variants. In addition, all studies used for
GWAS performed to date have limited representation of rare and infrequent risk-associated variants. The
NHLBI TOPMed program is now generating RNA-seq and proteomics data for thousands of TOPMed
participants with whole genome sequence (WGS) data. TOPMed specifically is enhanced with subjects of non-
European ancestry populations, thereby increasing ethnic diversity and including participants from the
population-based Multi-Ethnic Study of Atherosclerosis [MESA], the COPD-enriched COPDGene study, and
the Lung Tissue Research Consortium [LTRC]). We hypothesize systematic integration of multi-omic data with
novel rare/infrequent variant associations identified through TOPMed will accelerate discovery and validation of
novel biomarkers, definition of the molecular mechanisms underlying pathogenesis of COPD, and construction
of improved genetic risk models for diverse ancestry populations. To address these overarching hypotheses,
we propose two Specific Aims. In Aim 1, we will identify rare/infrequent and common variation underlying
PFT and COPD through expanded WGS analysis in TOPMed, perform multi-ancestry fine mapping, and
construct new genetic risk prediction models tailored to African ancestry and multi-ancestry
applications. In Aim 2, we will identify and validate candidate genes and molecular targets underlying
known and novel genetic associations for PFT / COPD through comprehensive multi-omic and
functional studies. To accomplish these Aims, we will combine the most current methods for WGS analysis
with novel multi-omics approaches to leverage our large-scale high quality RNA-seq and proteomic resources.
We have assembled an interdisciplinary collaborative group representing expertise in statistical genetics,
pulmonary epidemiology, integrative genomics, proteomics, and pulmonary medicine. Completion of these
Aims will establish an expanded view of rare and common genetic variation and their downstream molecular
...

## Key facts

- **NIH application ID:** 10462601
- **Project number:** 5R01HL153248-02
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** MICHAEL H. CHO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $758,323
- **Award type:** 5
- **Project period:** 2021-08-15 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10462601

## Citation

> US National Institutes of Health, RePORTER application 10462601, Integrative genomic, transcriptomic and proteomic studies of pulmonary function and COPD (5R01HL153248-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10462601. Licensed CC0.

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