# Project 03:  Genetics of Sleep Apnea and Its Consequences

> **NIH NIH P01** · UNIVERSITY OF PENNSYLVANIA · 2020 · $426,113

## Abstract

ABSTRACT
 Obstructive sleep apnea (OSA) is a common disorder whose prevalence is increasing. Sleep apnea is
a systemic disorder, with recurrent falls in oxygen (hypoxia) and reoxygenation (oxidative stress) affecting
every tissue. Thus, sleep apnea is an independent risk factor for cardiovascular disease (heart attack and
stroke), hypertension, cognitive impairment and dementia, and cancer. However, there are major individual
differences, with some individuals even with severe OSA not developing any of these consequences. While it
has been known for two decades that OSA aggregates in families, no convincing gene variants conferring risk
have been identified in human studies. This suggests that a new approach is required. The study we propose
introduces the following new approaches: a) it will be conducted in mice as a model system. Mice have proven
to be a powerful model system to identify gene variants for human disease; we will use the recently described
Diversity Outbred strategy that identifies quantitative trait loci of the order of three genes. This requires high
throughput phenotyping of large numbers of genetically heterogeneous mice in combination with genotyping by
a universal mouse SNP chip; b) we will study key endophenotypes that confer risk to OSA—tongue fat and
ventilatory responses to hypoxia and hypercapnia. We will assess heritability of each of these traits and
determine if tongue fat is a unique fat distribution; and c) we will assess the blood pressure response to cyclical
intermittent hypoxia that simulates the pattern of deoxygenation/reoxygenation that occurs in patients with
OSA. For all phenotypes assessed, functional assessment of genes identified will be performed. Thus, the
study introduces an entirely novel approach to identifying gene variants and performing a functional
assessment of genes for all phenotypes assessed. Large numbers of human samples with well phenotyped
individuals are already in hand to translate findings from these mouse studies to humans, and in particular the
phenotypes being assessed in these mouse studies are being assessed in a quantitative manner in the two
human projects (Projects 01, 02). Sequencing of genes identified will be performed in the samples from the
other projects in the Program Project Grant.

## Key facts

- **NIH application ID:** 9978115
- **Project number:** 5P01HL094307-10
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Allan I Pack
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $426,113
- **Award type:** 5
- **Project period:** — → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9978115

## Citation

> US National Institutes of Health, RePORTER application 9978115, Project 03:  Genetics of Sleep Apnea and Its Consequences (5P01HL094307-10). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9978115. Licensed CC0.

---

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