An integrated multi-omics analysis of sleep-disordered breathing traits implicates P2XR4 purinergic signaling

Nuzulul Kurniansyah; Danielle A Wallace; Ying Zhang; Bing Yu; Brian Cade; Heming Wang; Heather M Ochs-Balcom; Alexander P Reiner; Alberto R Ramos; Joshua D Smith; Jianwen Cai; Martha Daviglus; Phyllis C Zee; Robert Kaplan; Charles Kooperberg; Stephen S Rich; Jerome I Rotter; Sina A Gharib; Susan Redline; Tamar Sofer

doi:10.1038/s42003-023-04520-y

An integrated multi-omics analysis of sleep-disordered breathing traits implicates P2XR4 purinergic signaling

Commun Biol. 2023 Jan 31;6(1):125. doi: 10.1038/s42003-023-04520-y.

Authors

Nuzulul Kurniansyah¹, Danielle A Wallace¹, Ying Zhang¹, Bing Yu², Brian Cade^{1

3

4}, Heming Wang^{1

3

4}, Heather M Ochs-Balcom⁵, Alexander P Reiner^{5

6}, Alberto R Ramos⁷, Joshua D Smith⁸, Jianwen Cai⁹, Martha Daviglus¹⁰, Phyllis C Zee¹¹, Robert Kaplan^{12

13}, Charles Kooperberg¹², Stephen S Rich¹⁴, Jerome I Rotter¹⁵, Sina A Gharib¹⁶, Susan Redline^{1

4}, Tamar Sofer^{17

18

19}

Affiliations

¹ Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA, USA.
² Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA.
³ The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
⁴ Division of Sleep Medicine, Harvard Medical School, Boston, MA, USA.
⁵ Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, University at Buffalo, The State University of New York, Buffalo, NY, USA.
⁶ Department of Epidemiology, University of Washington, Seattle, WA, USA.
⁷ Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, USA.
⁸ Northwest Genomic Center, University of Washington, Seattle, WA, USA.
⁹ Department of Biostatistics, University of North Carolina, at Chapel Hill, NC, USA.
¹⁰ Institute for Minority Health Research, University of Illinois at Chicago, Chicago, IL, USA.
¹¹ Division of Sleep Medicine, Department of Neurology, Northwestern University, Chicago, IL, USA.
¹² Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA.
¹³ Department of Epidemiology & Population Health, Department of Pediatrics, Albert Einstein College of Medicine, Bronx, NY, USA.
¹⁴ Center for Public Health Genomics, University of Virginia School of Medicine, Charlottesville, VA, USA.
¹⁵ The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
¹⁶ Computational Medicine Core, Center for Lung Biology, UW Medicine Sleep Center, Department of Medicine, University of Washington, Seattle, WA, USA.
¹⁷ Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA, USA. [email protected].
¹⁸ Division of Sleep Medicine, Harvard Medical School, Boston, MA, USA. [email protected].
¹⁹ Departments of Medicine and of Biostatistics, Harvard University, Boston, MA, USA. [email protected].

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Hispanic or Latino
Humans
Multifactorial Inheritance
Multiomics*
Oxyhemoglobins
Receptors, Purinergic P2X7
Sleep
Sleep Apnea Syndromes* / genetics

Substances

P2RX7 protein, human
Oxyhemoglobins
Receptors, Purinergic P2X7
butyrylcarnitine

Abstract

Publication types

MeSH terms

Substances

Grants and funding