# Individual Differences in Obstructive Sleep Apnea

> **NIH NIH P01** · UNIVERSITY OF PENNSYLVANIA · 2020 · $2,344,415

## Abstract

DESCRIPTION (Provided by applicant):    
Sleep apnea is a systematic disorder. All tissues in the body experience hypoxia that occurs as a consequence of apneas. Thus, sleep apnea leads to multiple adverse consequences. Sleep apnea is heritable, although to date no convincing gene variants have been identified. There are also important individual differences in risks and consequences within patients. These individual differences suggest that sleep apnea is an ideal disorder to develop a PERSONALIZED approach to risk assessment, diagnosis and management. It is this overall concept that motivates this program of research. The program has 3 projects and 5 supporting cores. The first project-Mechanisms  of  Extreme  Phenotypes  in  Obstructive  Sleep  Apnea  (OSA)  (Project  Leader:  R. Schwab)-is focused on understanding the basis of extreme phenotypes. In this project the investigators study very obese individuals with and without sleep apnea. They ask the question-given that these individuals have the major risk for sleep apnea, what protects those without the disorder? Is it a difference in fat distribution, different physiological control mechanisms or a combination? The investigators also study lean individuals with and without sleep apnea and ask the same question-why? What role does craniofacial structure, different distributions  of  fat  and  ventilatory  control  system  instablity  play  in  the  development  of  apnea  in  thin individuals? This project is based on in-depth phenotyping. Project 02-Mechanisms for Individual Differences in Hypertension in Obstructive Sleep Apnea (Project Leader: S. Kuna)-addresses the basis of individual differences in blood pressure response to sleep apnea. The investigators propose that the largest effect of sleep apnea on blood pressure will occur in individuals whose BP is not controlled on anti-hypertensive medications, and that these individuals will benefit most from PAP treatment. They ask the question-why? The investigators propose that the individual differences in blood pressure response are related to individual differences in oxidative stress and catecholamine responses to sleep apnea. They predict that these proposed mediators are  driven by  genetic differences in  the  key  enzyme that  leads to  oxidative stress-NADPH oxidase-and propose sequencing of genes that regulate activity of this enzyme. The final project-Genetics of Sleep Apnea and Its Consequences (Project Leader: A. Pack)-continues the genetic theme, but proposes a new strategy to identify genes conferring risk for sleep apnea and its consequences. This strategy involves mice, in particular the genetically heterogeneous Diversity Outbred mice, a recently developed, state-of-the-art approach to genetic discovery through animal models that has already shown its ability to discover new genetic associations. High throughput phenotyping of these mice, together with genotyping with a genome-wide SNP chip, allows identification of smal...

## Key facts

- **NIH application ID:** 9978082
- **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:** $2,344,415
- **Award type:** 5
- **Project period:** 2009-07-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9978082

## Citation

> US National Institutes of Health, RePORTER application 9978082, Individual Differences in Obstructive Sleep Apnea (5P01HL094307-10). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9978082. Licensed CC0.

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