Metabolomic profiles of sleep-disordered breathing are associated with hypertension and diabetes mellitus development

Ying Zhang; Bing Yu; Qibin Qi; Ali Azarbarzin; Han Chen; Neomi A Shah; Alberto R Ramos; Phyllis C Zee; Jianwen Cai; Martha L Daviglus; Eric Boerwinkle; Robert Kaplan; Peter Y Liu; Susan Redline; Tamar Sofer

doi:10.1038/s41467-024-46019-y

Metabolomic profiles of sleep-disordered breathing are associated with hypertension and diabetes mellitus development

Nat Commun. 2024 Feb 28;15(1):1845. doi: 10.1038/s41467-024-46019-y.

Authors

Ying Zhang¹, Bing Yu², Qibin Qi³, Ali Azarbarzin⁴, Han Chen⁵, Neomi A Shah⁶, Alberto R Ramos⁷, Phyllis C Zee⁸, Jianwen Cai⁹, Martha L Daviglus¹⁰, Eric Boerwinkle², Robert Kaplan^{3

11}, Peter Y Liu¹², Susan Redline⁴, Tamar Sofer^{13

14

15}

Affiliations

¹ Division of Sleep Medicine and Circadian Disorders, Department of Medicine, Brigham and Women's Hospital, Boston, MA, 02115, USA.
² Department of Epidemiology, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA.
³ Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, NY, USA.
⁴ Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham & Women's Hospital & Harvard Medical School, Boston, MA, 02115, USA.
⁵ Human Genetics Center, Department of Epidemiology, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA.
⁶ Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
⁷ Sleep Medicine Program, Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, 33136, USA.
⁸ Division of Sleep Medicine, Department of Neurology, Northwestern University, Chicago, IL, 60611, USA.
⁹ Collaborative Studies Coordinating Center, Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
¹⁰ Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, 60612, USA.
¹¹ Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA.
¹² The Institute for Translational Genomics and Population Sciences, The Lundquist Institute at Harbor-UCLA Medical Center, Torrance, CA, 90502, USA.
¹³ Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham & Women's Hospital & Harvard Medical School, Boston, MA, 02115, USA. tsofer@bidmc.harvard.edu.
¹⁴ Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, 02115, USA. tsofer@bidmc.harvard.edu.
¹⁵ CardioVascular Institute, Beth Israel Deaconess Medical Center, Boston, MA, 02115, USA. tsofer@bidmc.harvard.edu.

Abstract

Sleep-disordered breathing (SDB) is a prevalent disorder characterized by recurrent episodic upper airway obstruction. Using data from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), we apply principal component analysis (PCA) to seven SDB-related measures. We estimate the associations of the top two SDB PCs with serum levels of 617 metabolites, in both single-metabolite analysis, and a joint penalized regression analysis. The discovery analysis includes 3299 individuals, with validation in a separate dataset of 1522 individuals. Five metabolite associations with SDB PCs are discovered and replicated. SDB PC1, characterized by frequent respiratory events common in older and male adults, is associated with pregnanolone and progesterone-related sulfated metabolites. SDB PC2, characterized by short respiratory event length and self-reported restless sleep, enriched in young adults, is associated with sphingomyelins. Metabolite risk scores (MRSs), representing metabolite signatures associated with the two SDB PCs, are associated with 6-year incident hypertension and diabetes. These MRSs have the potential to serve as biomarkers for SDB, guiding risk stratification and treatment decisions.

MeSH terms

Aged
Diabetes Mellitus*
Humans
Hypertension* / complications
Male
Regression Analysis
Risk Factors
Sleep Apnea Syndromes*
Young Adult

Abstract

MeSH terms

Grants and funding