Development and validation of a metabolite index for obstructive sleep apnea across race/ethnicities
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 fo...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-12-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-26321-9 |
| _version_ | 1811292633873514496 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Ying Zhang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T04:48:18Z |
| format | Article |
| id | doaj.art-e408e2ad0c324f20aabed8f931dfef2d |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-13T04:48:18Z |
| publishDate | 2022-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-e408e2ad0c324f20aabed8f931dfef2d2022-12-22T03:01:47ZengNature PortfolioScientific Reports2045-23222022-12-0112111510.1038/s41598-022-26321-9Development and validation of a metabolite index for obstructive sleep apnea across race/ethnicitiesYing Zhang0Debby Ngo1Bing Yu2Neomi A. Shah3Han Chen4Alberto R. Ramos5Phyllis C. Zee6Russell Tracy7Peter Durda8Robert Kaplan9Martha L. Daviglus10Stephen S. Rich11Jerome I. Rotter12Jianwen Cai13Clary Clish14Robert Gerszten15Bruce S. Kristal16Sina A. Gharib17Susan Redline18Tamar Sofer19Division of Sleep Medicine and Circadian Disorders, Department of Medicine, Brigham and Women’s HospitalDivision of Pulmonary, Critical Care and Sleep Medicine, Beth Israel Deaconess Medical Center, Cardiovascular InstituteDepartment of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, Human Genetics Center, The University of Texas Health Science Center at HoustonDepartment of Medicine, Albert Einstein College of MedicineDepartment of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, Human Genetics Center, The University of Texas Health Science Center at HoustonSleep Medicine Program, Department of Neurology, University of Miami Miller School of MedicineDivision of Sleep Medicine, Department of Neurology, Northwestern UniversityDepartment of Pathology Laboratory Medicine, Larner College of Medicine, University of VermontDepartment of Pathology Laboratory Medicine, Larner College of Medicine, University of VermontDepartment of Epidemiology & Population Health, Albert Einstein College of MedicineDepartment of Preventive Medicine, Northwestern University Feinberg School of MedicineCenter for Public Health Genomics, University of VirginiaDepartment of Pediatrics, The Institute for Translational Genomics and Population Sciences, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical CenterDepartment of Biostatistics, Collaborative Studies Coordinating Center, University of North Carolina at Chapel HillMetabolite Profiling Platform, Broad Institute of MIT and HarvardCardiovascular Research Center, Massachusetts General Hospital, Harvard Medical SchoolDepartment of Medicine, Sleep and Circadian Disorders, Harvard Medical SchoolDivision of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, University of WashingtonDepartment of Medicine, Division of Sleep Medicine and Circadian Disorders, Brigham and Women’s Hospital and Harvard Medical SchoolDepartment of Medicine, Sleep and Circadian Disorders, Harvard Medical SchoolAbstract 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.https://doi.org/10.1038/s41598-022-26321-9 |
| spellingShingle | 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 Development and validation of a metabolite index for obstructive sleep apnea across race/ethnicities Scientific Reports |
| title | Development and validation of a metabolite index for obstructive sleep apnea across race/ethnicities |
| title_full | Development and validation of a metabolite index for obstructive sleep apnea across race/ethnicities |
| title_fullStr | Development and validation of a metabolite index for obstructive sleep apnea across race/ethnicities |
| title_full_unstemmed | Development and validation of a metabolite index for obstructive sleep apnea across race/ethnicities |
| title_short | Development and validation of a metabolite index for obstructive sleep apnea across race/ethnicities |
| title_sort | development and validation of a metabolite index for obstructive sleep apnea across race ethnicities |
| url | https://doi.org/10.1038/s41598-022-26321-9 |
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