Abstract

Sleep Disordered Breathing (SDB) is a common disease associated with increased risk for cardiometabolic, cardiovascular, and cognitive diseases. How SDB affects the molecular environment is still poorly understood. We study the association of three SDB measures with gene expression measured using RNA-seq in multiple blood tissues from the Multi-Ethnic Study of Atherosclerosis. We develop genetic instrumental variables for the associated transcripts as polygenic risk scores (tPRS), then generalize and validate the tPRS in the Women’s Health Initiative. We measure the associations of the validated tPRS with SDB and serum metabolites in Hispanic Community Health Study/Study of Latinos. Here we find differential gene expression by blood cell type in relation to SDB traits and link P2XR4 expression to average oxyhemoglobin saturation during sleep and butyrylcarnitine (C4) levels. These findings can be used to develop interventions to alleviate the effect of SDB on the human molecular environment.

An integrated multi-omics analysis identifies an association chain among sleep-disordered breathing (SDB) traits, gene expression in circulating leukocytes, and serum metabolites, and supports a mechanistic role for P2XR4 purinergic signaling in SDB.

Details

Title
An integrated multi-omics analysis of sleep-disordered breathing traits implicates P2XR4 purinergic signaling
Author
Kurniansyah, Nuzulul 1 ; Wallace, Danielle A. 1   VIAFID ORCID Logo  ; Zhang, Ying 1 ; Yu, Bing 2 ; Cade, Brian 3   VIAFID ORCID Logo  ; Wang, Heming 3   VIAFID ORCID Logo  ; Ochs-Balcom, Heather M. 4   VIAFID ORCID Logo  ; Reiner, Alexander P. 5   VIAFID ORCID Logo  ; Ramos, Alberto R. 6 ; Smith, Joshua D. 7 ; Cai, Jianwen 8   VIAFID ORCID Logo  ; Daviglus, Martha 9 ; Zee, Phyllis C. 10 ; Kaplan, Robert 11 ; Kooperberg, Charles 12   VIAFID ORCID Logo  ; Rich, Stephen S. 13   VIAFID ORCID Logo  ; Rotter, Jerome I. 14 ; Gharib, Sina A. 15 ; Redline, Susan 16   VIAFID ORCID Logo  ; Sofer, Tamar 17   VIAFID ORCID Logo 

1  Brigham and Women’s Hospital, Division of Sleep and Circadian Disorders, Boston, USA (GRID:grid.62560.37) (ISNI:0000 0004 0378 8294) 
2  The University of Texas Health Science Center at Houston, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, Houston, USA (GRID:grid.267308.8) (ISNI:0000 0000 9206 2401) 
3  Brigham and Women’s Hospital, Division of Sleep and Circadian Disorders, Boston, USA (GRID:grid.62560.37) (ISNI:0000 0004 0378 8294); The Broad Institute of MIT and Harvard, Cambridge, USA (GRID:grid.66859.34) (ISNI:0000 0004 0546 1623); Harvard Medical School, Division of Sleep Medicine, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X) 
4  University at Buffalo, The State University of New York, Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, Buffalo, USA (GRID:grid.273335.3) (ISNI:0000 0004 1936 9887) 
5  University at Buffalo, The State University of New York, Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, Buffalo, USA (GRID:grid.273335.3) (ISNI:0000 0004 1936 9887); University of Washington, Department of Epidemiology, Seattle, USA (GRID:grid.34477.33) (ISNI:0000000122986657) 
6  University of Miami Miller School of Medicine, Department of Neurology, Miami, USA (GRID:grid.26790.3a) (ISNI:0000 0004 1936 8606) 
7  University of Washington, Northwest Genomic Center, Seattle, USA (GRID:grid.34477.33) (ISNI:0000000122986657) 
8  University of North Carolina, Department of Biostatistics, at Chapel Hill, USA (GRID:grid.410711.2) (ISNI:0000 0001 1034 1720) 
9  University of Illinois at Chicago, Institute for Minority Health Research, Chicago, USA (GRID:grid.185648.6) (ISNI:0000 0001 2175 0319) 
10  Northwestern University, Division of Sleep Medicine, Department of Neurology, Chicago, USA (GRID:grid.16753.36) (ISNI:0000 0001 2299 3507) 
11  Fred Hutchinson Cancer Center, Division of Public Health Sciences, Seattle, USA (GRID:grid.270240.3) (ISNI:0000 0001 2180 1622); Albert Einstein College of Medicine, Department of Epidemiology & Population Health, Department of Pediatrics, Bronx, USA (GRID:grid.251993.5) (ISNI:0000000121791997) 
12  Fred Hutchinson Cancer Center, Division of Public Health Sciences, Seattle, USA (GRID:grid.270240.3) (ISNI:0000 0001 2180 1622) 
13  University of Virginia School of Medicine, Center for Public Health Genomics, Charlottesville, USA (GRID:grid.27755.32) (ISNI:0000 0000 9136 933X) 
14  The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, Torrance, USA (GRID:grid.513199.6) 
15  University of Washington, Computational Medicine Core, Center for Lung Biology, UW Medicine Sleep Center, Department of Medicine, Seattle, USA (GRID:grid.34477.33) (ISNI:0000000122986657) 
16  Brigham and Women’s Hospital, Division of Sleep and Circadian Disorders, Boston, USA (GRID:grid.62560.37) (ISNI:0000 0004 0378 8294); Harvard Medical School, Division of Sleep Medicine, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X) 
17  Brigham and Women’s Hospital, Division of Sleep and Circadian Disorders, Boston, USA (GRID:grid.62560.37) (ISNI:0000 0004 0378 8294); Harvard Medical School, Division of Sleep Medicine, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X); Harvard University, Departments of Medicine and of Biostatistics, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X) 
Pages
125
Publication year
2023
Publication date
2023
Publisher
Nature Publishing Group
e-ISSN
23993642
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s42003-023-04520-y
ProQuest document ID
2771199279
Copyright
© The Author(s) 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.