Developing a P4 medicine approach to obstructive sleep apnea

Active Project Grant Awarded Last action

Award ID
P01HL160471
Recipient
Awarding agency
Obligated
$7,129,816

Award facts

Assistance listing
93.837 Cardiovascular Diseases Research
Completion date 67% complete
Place of performance
Philadelphia, PA 19104, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
This program is directed at developing a new approach to OSA care based on the principles of precision medicine, with a focus on improving prediction, prevention and personalization. The program has 4 projects and 3 cores to support the work of the investigators. Project 01 (genetics of extreme phenotypes of OSA and associated upper airway anatomy) is focused on identifying both common and rare genetic variants that are associated with risk for OSA. Since OSA has multiple pathways to disease, identifying associated genetic variants is challenging. This project investigates gene variants associated with quantitative intermediate traits for the disorder. The focus is on structural risk factors-both craniofacial dimensions and soft tissues. A focus is on tongue FAT, a specific heritable distribution of FAT that mediates the effect of obesity in causing OSA. Machine learning approaches have been developed to allow quantification of traits of interest from a large number of relevant clinically-obtained CT and MR images in individuals with genetic data. Data from this project will be used in combination with data from ongoing genetic studies to develop a polygenic risk score (PRS) for OSA with wide-applicability. Project 02 (micrornas as biomarkers for obstructive sleep apnea) will study micrornas as a biomarker relevant to OSA using RNA sequencing of all short micrornas. Expression of micrornas is dynamic; they respond to multiple challenges, including hypoxia. Micrornas are being used in development of biomarkers in multiple areas, with supportive data in OSA, albeit in relatively small samples. Thus, we will employ a combination of a hypothesis-driven approach complimented by a broader discovery strategy. Biomarkers will be developed to help identify cases with OSA, as well as to assess effectiveness of therapy and to provide prognostic information about who with OSA will have blood pressure reduction with treatment. Project 03 (mechanisms that account for different symptom subtypes of OSA) will examine the physiological and multi-omics determinants of robustly validated symptom subtypes of OSA. There will be an emphasis on the excessively sleepy subtype, which has been shown to be at elevated cardiovascular risk. We will evaluate whether there are differences in physiological responses during sleep in the different subtypes and/or whether there are genetic, epigenetic, and metabolomic differences. Project 04 (going from genetic associations to identification of causative genes) will focus on identifying causative genes that explain gwas associations. For genes conferring risk for OSA, we will begin with existing gwas data complimented by data from project 01. For sleepiness, this project will start with recently published genetic loci, and include analyses based on genes identified in project 03. We will first use cell-based approaches to identify possible causative genes. The role of these genes will be assessed in high-diversity mouse models (for genes associated with anatomy) and in drosophila and zebrafish (for genes associated with sleepiness).

Transactions

Action Obligated Date
Amendment $145,979
Amendment $0
Amendment $2,190,674
Amendment $2,292,560
Original award $2,500,603

Subawards

Subrecipient Amount Awarded
Geisinger Clinic "As site-PI for Geisinger, Dr. Anne Justice will provide oversight of the research program at the Geisinger site and will be responsible for the… $173,243
Geisinger Clinic Dr. Justice will oversee progress on all aims ensuring the successful completion of the proposed scope of work. Dr. Justice has been working with the… $129,805
University Of Iceland "The University of Iceland is a recruiting site for Project 02 in the Program Project - Developing a P4 Medicine approach to Obstructive Sleep Apnea. University… $145,979
University Of Kansas Medical Center Research Institute, Inc. Dr. Mazzotti is the Co-Director of the Data Integration Core. He will work closely with Drs. Holmes and Mowery as well as the Program Project leaders and Core… $50,795
Texas A & M University "Dr. Keene's duties on the project align with those outlined in the project description as well as supervising the research technician and graduate student. The… $139,268
The Ohio State University "The global hypothesis motivating Project 02 is that microRNAs are clinically-translatable biomarkers for improved case identification, measuring the efficacy… $137,920
The Children's Hospital Of Philadelphia "Dr. Grant is a Co-Investigator on this application and will work in partnership with the other investigators to contribute to this project. The expertise of… $124,758
Geisinger Clinic "As site-PI for Geisinger, Dr. Anne Justice will provide oversight of the research program at the Geisinger site and will be responsible for the… $240,798
Geisinger Clinic As site-PI for Geisinger, Dr. Anne Justice will provide oversight of the research program at the Geisinger site and will be responsible for the implementation… $240,798
The Governors Of The University Of Calgary The Hallgrimsson lab will perform a QTL analysis for craniofacial shape parameters relevant to sleep apnea on a sample of 1600 Diversity Outcross mice. This… $53,212
University Of Florida As co-I on this project, Dr. Robishaw will be critical for translating the genomics discoveries into a deep understanding of the underlying pathophysiologic… $26,744
The Ohio State University The global hypothesis motivating Project 02 is that microRNAs are clinically-translatable biomarkers for improved case identification, measuring the efficacy of… $135,161
University Of Iceland The University of Iceland is a recruiting site for Project 02 in the Program Project - Developing a P4 Medicine approach to Obstructive Sleep Apnea.… $142,522
The Ohio State University Aim 3 will apply integrative methods to combine sequencing data with multi-Omics data from TOPMed and Project 02 to identify potential causal genes and… $19,625
Cedars-Sinai Medical Center Dr. Ryan Urbanowicz at the Cedars-Sinai Medical Center will be responsible for providing machine learning and data mining expertise regarding the analysis,… $18,780
Texas A & M University Dr. Keene's duties on the project align with those outlined in the project description as well as supervising the research technician and graduate student.… $136,483
Geisinger Clinic Dr. Justice will oversee progress on all aims ensuring the successful completion of the proposed scope of work. Dr. Justice has been working with the… $169,440
The Children's Hospital Of Philadelphia Dr. Grant is a Co-Investigator on this application and will work in partnership with the other investigators to contribute to this project. The expertise of Dr.… $173,716
The Ohio State University The global hypothesis motivating Project 02 is that microRNAs are clinically-translatable biomarkers for improved case identification, measuring the efficacy of… $103,440
The Governors Of The University Of Calgary (See attached) $54,298
University Of Florida (See Attached) $27,290
Texas A & M University Dr. Keene's duties on the project align with those outlined in the project description as well as supervising the research technician and graduate student.… $139,268
University Of Iceland The University of Iceland is a recruiting site for Project 02 in the Program Project - Developing a P4 Medicine approach to Obstructive Sleep Apnea.… $145,979
Show all 23

Quick answers

Who received award P01HL160471?

P01HL160471 was awarded to The Trustees Of The University Of Pennsylvania by National Heart Lung and Blood Institute (National Institutes of Health) on July 1, 2023.

How much is award P01HL160471 worth?

$7,129,816 has been obligated on P01HL160471.

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