Development and validation of a metabolite index for obstructive sleep apnea across race/ethnicities
Year: 2022
Type: article
Study design: Observational Study
Abstract: Obstructive sleep apnea (OSA) is a common disorder characterized by recurrent episodes of upper airway obstruction during sleep resulting in oxygen desaturation and sleep fragmentation, and associated with increased risk of adverse health outcomes. Metabolites are being increasingly used for biomarker discovery and evaluation of disease processes and progression. Studying metabolomic associations with OSA in a diverse community-based cohort may provide insights into the pathophysiology of OSA. We aimed to develop and replicate a metabolite index for OSA and identify individual metabolites associated with OSA. We studied 219 metabolites and their associations with the apnea hypopnea index (AHI) and with moderate-severe OSA (AHI ≥ 15) in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) (n = 3507) using two methods: (1) association analysis of individual metabolites, and (2) least absolute shrinkage and selection operator (LASSO) regression to identify a subset of metabolites jointly associated with OSA, which was used to develop a metabolite index for OSA. Results were validated in the Multi-Ethnic Study of Atherosclerosis (MESA) (n = 475). When assessing the associations with individual metabolites, we identified seven metabolites significantly positively associated with OSA in HCHS/SOL (FDR p < 0.05), of which four associations-glutamate, oleoyl-linoleoyl-glycerol (18:1/18:2), linoleoyl-linoleoyl-glycerol (18:2/18:2) and phenylalanine, were replicated in MESA (one sided-p < 0.05). The OSA metabolite index, composed of 14 metabolites, was associated with a 50% increased risk for moderate-severe OSA (OR = 1.50 [95% CI 1.21-1.85] per 1 SD of OSA metabolite index, p < 0.001) in HCHS/SOL and 55% increased risk (OR = 1.55 [95% CI 1.10-2.20] per 1 SD of OSA metabolite index, p = 0.013) in MESA, both adjusted for demographics, lifestyle, and comorbidities. Similar albeit less significant associations were observed for AHI. Replication of the metabolite index in an independent multi-ethnic dataset demonstrates the robustness of metabolomic-based OSA index to population heterogeneity. Replicated metabolite associations may provide insights into OSA-related molecular and metabolic mechanisms.
Source: Scientific Reports
Authors: Ying Zhang, Debby Ngo, Bing Yu, Neomi A. Shah, Han Chen, Alberto R. Ramos, Phyllis C. Zee, Russell Tracy, Peter Durda, Robert Kaplan, Martha L. Daviglus, Stephen S. Rich, Jerome I. Rotter, Jianwen Cai, Clary Clish, Robert Gerszten, Bruce S. Kristal, Sina A. Gharib, Susan Redline, Tamar Sofer
Institutions: Brigham and Women's Hospital, Beth Israel Deaconess Medical Center, The University of Texas Health Science Center at Houston, Albert Einstein College of Medicine, University of Miami, Northwestern University, University of Vermont, University of Virginia, The Lundquist Institute, Harbor–UCLA Medical Center, University of North Carolina at Chapel Hill, Broad Institute, Harvard University, Massachusetts Institute of Technology, Massachusetts General Hospital, University of Washington
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,190
Funders: Office of Dietary Supplements, University of Miami, National Institutes of Health, National Institute on Aging, National Heart, Lung, and Blood Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, National Institute of Dental and Craniofacial Research, National Center for Advancing Translational Sciences, National Institute on Minority Health and Health Disparities
Awards: G1081972346, G1106073490, G1261793039, MESA, G1276754516, G1312369436, Hispanic Community Health Study, G1455175283, G1539384734, G1640378483, G1803853571, G2144938473, Rare variants and NHLBI traits in deeply phenotyped cohorts, G22458031, G232264632, MESA, G2466919156, HISPANIC COMMUNITY HEALTH STUDY - FIELD CENTER, G2580996367, G2644289446, MESA, G2837638605, G290884426, G291913881, SUBCLINICAL CARDIOVASCULAR DISEASE STUDY--EBCT READING, G297113894, G3181782377, Phenotypic and Molecular Signatures for Sleep Apnea and Related Morbidities, Hispanic Community Health Study, G343705321, G3549415863, G3570589137, G36937976, MESA, Rare variants and NHLBI traits in deeply phenotyped cohorts, TITLE: MULTI-ETHNIC STUDY OF ATHEROSCLEROSIS (MESA), Hispanic Community Health Study, G4429312988, G4563812999, OPTION 3. 4/1/2014 - 3/31/2015. MULTI-ETHNIC STUDY OF ATHEROSCLEROSIS (MESA) - READING CENTER, NHLBI, MESA, G50080621, G5108002584, G514410172, SUBCLINICAL CARDIOVASCULAR DISEASE STUDY-ULTRASOUND, HISPANIC COMMUNITY HEALTH STUDY - COORDINATING CENTER, Institute for Clinical and Translational Research, MESA, G66341962, SNP HEALTH ASSOCIATION RESOURCE (SHARE), MESA, G78770644, Clinical and Translational Science Award, Studies of Rare Genetic Variation in the Isolated Population of Sardinia, G8761005068, Diabetes Research Center (DRC), Leveraging omics data to understand sleep health and its consequences among diverse Hispanics/Latinos, Application of Machine Learning to Identify Obstructive Sleep Apnea Subgroups at Risk for Atherosclerosis Progression and Cardiovascular Disease Events (OSA-GRANDE), UCLA Clinical and Translational Science Institute, G913983815, G94668252, G991334795
OpenAlex ID: W4311902572