SynthesisPLoS genetics2019
Associations of variants In the hexokinase 1 and interleukin 18 receptor regions with oxyhemoglobin saturation during sleep.
Open access · goldAbstract readMeta-Analysis
In one paragraph
Synthesis in PLoS genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 2 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed, 2 pooled it
3.9field-weighted citation impact, top 6% of its field
What it found
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The trial behind it
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Who cites it
21 citing papers in PubMed, 2 syntheses or guidelines pooled it, 42 citations in OpenAlex.
- Genome-wide association study of obstructive sleep apnoea in the Million Veteran Program uncovers genetic heterogeneity by sex.EBioMedicine · 2023Pooled it
- Discovery of genomic loci associated with sleep apnea risk through multi-trait GWAS analysis with snoring.Sleep · 2023Pooled it
- Genetic associations between serotonin receptor 1F (The European respiratory journal · 2025Article
- Genomic dissection of sleep archetypes in a large autism cohort.medRxiv : the preprint server for health sciences · 2025Article
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- Genetic Predisposition to Elevated C-Reactive Protein and Risk of Obstructive Sleep Apnea.American journal of respiratory and critical care medicine · 2024Article
- International Consensus Statement on Obstructive Sleep Apnea.International forum of allergy & rhinology · 2023Review
- Genetics of circadian rhythms and sleep in human health and disease.Nature reviews. Genetics · 2023Review
- Leveraging pleiotropy to discover and interpret GWAS results for sleep-associated traits.PLoS genetics · 2022Article
- Targeted Genome Sequencing Identifies Multiple Rare Variants in Caveolin-1 Associated with Obstructive Sleep Apnea.American journal of respiratory and critical care medicine · 2022Article
- Article
- Upregulated heme biosynthesis increases obstructive sleep apnea severity: a pathway-based Mendelian randomization study.Scientific reports · 2022Article
- Neuroinflammation, Sleep, and Circadian Rhythms.Frontiers in cellular and infection microbiology · 2022Review
- Whole-genome association analyses of sleep-disordered breathing phenotypes in the NHLBI TOPMed program.Genome medicine · 2021Article
- Association ofJournal of clinical medicine · 2021Article
- Article
- Cutting the fat: advances and challenges in sleep apnoea genetics.The European respiratory journal · 2021Article
- Proteomic biomarkers of sleep apnea.Sleep · 2020Article
- Insights into the aetiology of snoring from observational and genetic investigations in the UK Biobank.Nature communications · 2020Article
- More Than the Sum of the Respiratory Events: Personalized Medicine Approaches for Obstructive Sleep Apnea.American journal of respiratory and critical care medicine · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
47 authors at 20 institutions in 2 countries.
Brian E CadeDivision of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA, United States of America.ORCID 0000-0003-1424-0673
Han ChenHuman Genetics Center, Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX United States of America.ORCID 0000-0002-9510-4923
Adrienne M StilpDepartment of Biostatistics, University of Washington, Seattle, WA United States of America.
Tin LouieDepartment of Biostatistics, University of Washington, Seattle, WA United States of America.
Sonia Ancoli-IsraelDepartment of Psychiatry, University of California, San Diego, CA, United States of America.
Raanan ArensThe Children's Hospital at Montefiore, Division of Respiratory and Sleep Medicine, Albert Einstein College of Medicine, Bronx, NY, United States of America.
Richard BarfieldDepartment of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, United States of America.ORCID 0000-0002-6276-7704
Jennifer E BelowVanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, United States of America.
Jianwen CaiDepartment of Biostatistics, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, United States of America.
Matthew P ConomosDepartment of Biostatistics, University of Washington, Seattle, WA United States of America.
Daniel S EvansCalifornia Pacific Medical Center Research Institute, San Francisco, CA, United States of America.
Alexis C Frazier-WoodUSDA/ARS Children's Nutrition Research Center, Baylor College of Medicine, Houston, TX, United States of America.
Sina A GharibComputational Medicine Core, Center for Lung Biology, UW Medicine Sleep Center, Division of Pulmonary, Critical Care and Sleep Medicine, University of Washington, Seattle WA, United States of America.
Kevin J GleasonDivision of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA, United States of America.
Daniel J GottliebDivision of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA, United States of America.ORCID 0000-0001-8812-8751
David R HillmanDepartment of Pulmonary Physiology and Sleep Medicine, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia.
W Craig JohnsonDepartment of Biostatistics, University of Washington, Seattle, WA United States of America.
David J LedererDepartments of Medicine and Epidemiology, Columbia University, New York, NY, United States of America.ORCID 0000-0001-5258-0228
Jiwon LeeDivision of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA, United States of America.ORCID 0000-0002-4079-7494
Jose S LoredoDivision of Pulmonary Critical Care and Sleep Medicine, Department of Medicine, UC San Diego School of Medicine, La Jolla, CA, United States of America.
Hao MeiDepartment of Data Science, University of Mississippi Medical Center, Jackson, MS, United States of America.
Sutapa MukherjeeSleep Health Service, Respiratory and Sleep Services, Southern Adelaide Local Health Network, Adelaide, South Australia.ORCID 0000-0001-5021-1648
Sanjay R PatelDivision of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, United States of America.ORCID 0000-0002-9142-5172
Wendy S PostDivision of Cardiology, Johns Hopkins University, Baltimore, MD, United States of America.
Shaun M PurcellDivision of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA, United States of America.
Alberto R RamosDepartment of Neurology, University of Miami Miller School of Medicine, Miami, FL, United States of America.
Kathryn J ReidDepartment of Neurology, Center for Circadian and Sleep Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, United States of America.
Ken RiceDepartment of Biostatistics, University of Washington, Seattle, WA United States of America.
Neomi A ShahDivision of Pulmonary, Critical Care and Sleep Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States of America.
Tamar SoferDivision of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA, United States of America.ORCID 0000-0001-8520-8860
Kent D TaylorThe Institute for Translational Genomics and Population Sciences, Departments of Pediatrics and Medicine, LABioMed at Harbor-UCLA Medical Center, Torrance, CA, United States of America.
Timothy A ThorntonDepartment of Biostatistics, University of Washington, Seattle, WA United States of America.
Heming WangDivision of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA, United States of America.
Kristine YaffeDepartment of Psychiatry, Neurology, and Epidemiology and Biostatistics, University of California at San Francisco, San Francisco, CA, United States of America.
Phyllis C ZeeDepartment of Neurology, Center for Circadian and Sleep Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, United States of America.
Craig L HanisHuman Genetics Center, Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX United States of America.ORCID 0000-0002-4880-5348
Lyle J PalmerSchool of Public Health, University of Adelaide, South Australia, Australia.ORCID 0000-0002-1628-3055
Jerome I RotterThe Institute for Translational Genomics and Population Sciences, Departments of Pediatrics and Medicine, LABioMed at Harbor-UCLA Medical Center, Torrance, CA, United States of America.ORCID 0000-0001-7191-1723
Katie L StoneCalifornia Pacific Medical Center Research Institute, San Francisco, CA, United States of America.
Gregory J TranahCalifornia Pacific Medical Center Research Institute, San Francisco, CA, United States of America.
James G WilsonDepartment of Physiology and Biophysics, University of Mississippi Medical Center, Jackson MS, United States of America.
Shamil R SunyaevProgram in Medical and Population Genetics, Broad Institute, Cambridge, MA, United States of America.
Cathy C LaurieDepartment of Biostatistics, University of Washington, Seattle, WA United States of America.ORCID 0000-0003-2572-4040
Xiaofeng ZhuDepartment of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, United States of America.
Richa SaxenaDivision of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA, United States of America.
Xihong LinDepartment of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, United States of America.
Susan RedlineDivision of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA, United States of America.
University of Washington · USBrigham and Women's Hospital · USBroad Institute · USCalifornia Pacific Medical Center · USHarvard University · USJackson Memorial Hospital · USNorthwestern University · USThe Lundquist Institute · USThe University of Texas Health Science Center at Houston · USUniversity of California San Diego · USAlbert Einstein College of Medicine · USCase Western Reserve University · USChildren's Nutrition Research Center at Baylor College of Medicine · USColumbia University · USFlinders University · AUIcahn School of Medicine at Mount Sinai · USJohns Hopkins University · USSan Francisco VA Medical Center · USSir Charles Gairdner Hospital · AUThe University of Adelaide · AU
Funding
UCLA Clinical Translational Science InstituteUL1TR001881 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARLEEN F. BROWN, ARASH NAEIM · 2016 to 2026
$118.1MInstitute for Clinical and Translational ResearchUL1TR001079 · NCATS · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2013 to 2017
$60.1MUCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0MTransgenic & Knock-out MouseP30DK063491 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ALAN R. SALTIEL · 2003 to 2026
$40.4MTracking and Evaluation CoreU54GM115428 · NIGMS · UNIVERSITY OF MISSISSIPPI MED CTR · PI LIRETTE, SETH · 2016 to 2025
$38.2MUNC-CH CENTER FOR ENVIRONMENTAL HEALTH &SUSCEPTIBILITYP30ES010126 · NIEHS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Hazel B Nichols · 2001 to 2026
$36.3MWake Forest Clinical and Translational Science AwardUL1TR001420 · NCATS · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI ARD, JAMY D, FOLEY, KRISTIE L · 2015 to 2023
$32.3MOregon Clinical and Translational Research InstituteUL1TR000128 · NCATS · OREGON HEALTH & SCIENCE UNIVERSITY · PI ELLISON, DAVID H · 2012 to 2015
$28.7MClinical and Translational Science AwardUL1TR000040 · NCATS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GINSBERG, HENRY N · 2012 to 2015
$26.2MVascular Effects of Heparan Sulfate ProteoglycansP50HL056984 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI TABAS, IRA A · 1997 to 2006
$13.1MOutcomes of Sleep Disorders in Older MenR01HL071194 · NHLBI · UNIVERSITY OF CALIFORNIA SAN FRANCISCO · PI STONE, KATIE L · 2003 to 2013
$12.2MCase Western Reserve University/Cleveland Clinic CTSA (KL2)KL2RR024990 · NCRR · CASE WESTERN RESERVE UNIVERSITY · PI DAVIS, PAMELA B · 2007 to 2011
$9.5MNCATS NIH HHS UL1 TR000040NCATS NIH HHS UL1 TR000124NCATS NIH HHS UL1 TR000128NCATS NIH HHS UL1 TR001079NCATS NIH HHS UL1 TR001420NCATS NIH HHS UL1 TR001881NCRR NIH HHS KL2 RR024990NHGRI NIH HHS HHSN268201300003CNHLBI NIH HHS HHSN268200800007CNHLBI NIH HHS HHSN268201200036CNHLBI NIH HHS HHSN268201300001CNHLBI NIH HHS HHSN268201300003INHLBI NIH HHS HHSN268201300004CNHLBI NIH HHS HHSN268201300005CNHLBI NIH HHS HHSN268201300046CNHLBI NIH HHS HHSN268201300047CNHLBI NIH HHS HHSN268201300048CNHLBI NIH HHS HHSN268201300049CNHLBI NIH HHS HHSN268201300050CNHLBI NIH HHS HHSN268201500003CNHLBI NIH HHS HHSN268201500003INHLBI NIH HHS K01 HL135405NHLBI NIH HHS N01 HC025195NHLBI NIH HHS N01 HC055015NHLBI NIH HHS N01 HC055016NHLBI NIH HHS N01 HC055018NHLBI NIH HHS N01 HC055019NHLBI NIH HHS N01 HC055020NHLBI NIH HHS N01 HC055021NHLBI NIH HHS N01 HC055222NHLBI NIH HHS N01 HC065233NHLBI NIH HHS N01 HC065234NHLBI NIH HHS N01 HC065235NHLBI NIH HHS N01 HC065236NHLBI NIH HHS N01 HC065237NHLBI NIH HHS N01 HC085079NHLBI NIH HHS N01 HC085080NHLBI NIH HHS N01 HC085081NHLBI NIH HHS N01 HC085082NHLBI NIH HHS N01 HC085083NHLBI NIH HHS N01 HC085086NHLBI NIH HHS N01 HC095159NHLBI NIH HHS N01 HC095160NHLBI NIH HHS N01 HC095161NHLBI NIH HHS N01 HC095162NHLBI NIH HHS N01 HC095163NHLBI NIH HHS N01 HC095164NHLBI NIH HHS N01 HC095165NHLBI NIH HHS N01 HC095166NHLBI NIH HHS N01 HC095167NHLBI NIH HHS N01 HC095168NHLBI NIH HHS N01 HC095169NHLBI NIH HHS N02 HL064278NHLBI NIH HHS P50 HL056984NHLBI NIH HHS R01 HL046380NHLBI NIH HHS R01 HL070837NHLBI NIH HHS R01 HL070838NHLBI NIH HHS R01 HL070839NHLBI NIH HHS R01 HL070841NHLBI NIH HHS R01 HL070842NHLBI NIH HHS R01 HL070847NHLBI NIH HHS R01 HL070848NHLBI NIH HHS R01 HL071194NHLBI NIH HHS R01 HL085251NHLBI NIH HHS R01 HL087652NHLBI NIH HHS R01 HL098433NHLBI NIH HHS R01 HL102830NHLBI NIH HHS R01 HL103612NHLBI NIH HHS R01 HL105756NHLBI NIH HHS R01 HL110068NHLBI NIH HHS R01 HL113338NHLBI NIH HHS R01 HL120393NHLBI NIH HHS R21 HL140437NHLBI NIH HHS R35 HL135818NHLBI NIH HHS U01 HL053941NHLBI NIH HHS U01 HL080295NHLBI NIH HHS U01 HL130114NIAID NIH HHS R01 AI085014NIAMS NIH HHS R01 AR051124NIAMS NIH HHS RC2 AR058973NIAMS NIH HHS U01 AR066160NIA NIH HHS R01 AG023629NIA NIH HHS R21 AG056952NIA NIH HHS U01 AG027810NIA NIH HHS U01 AG042124NIA NIH HHS U01 AG042139NIA NIH HHS U01 AG042140NIA NIH HHS U01 AG042143NIA NIH HHS U01 AG042145NIA NIH HHS U01 AG042168NICHD NIH HHS U54 HD083211NIDDK NIH HHS P30 DK063491NIDDK NIH HHS R01 DK073541NIDDK NIH HHS U01 DK085501NIEHS NIH HHS P30 ES010126NIGMS NIH HHS U54 GM115428
Abstract
Sleep disordered breathing (SDB)-related overnight hypoxemia is associated with cardiometabolic disease and other comorbidities. Understanding the genetic bases for variations in nocturnal hypoxemia may help understand mechanisms influencing oxygenation and SDB-related mortality. We conducted genome-wide association tests across 10 cohorts and 4 populations to identify genetic variants associated with three correlated measures of overnight oxyhemoglobin saturation: average and minimum oxyhemoglobin saturation during sleep and the percent of sleep with oxyhemoglobin saturation under 90%. The discovery sample consisted of 8,326 individuals. Variants with p < 1 × 10(-6) were analyzed in a replication group of 14,410 individuals. We identified 3 significantly associated regions, including 2 regions in multi-ethnic analyses (2q12, 10q22). SNPs in the 2q12 region associated with minimum SpO2 (rs78136548 p = 2.70 × 10(-10)). SNPs at 10q22 were associated with all three traits including average SpO2 (rs72805692 p = 4.58 × 10(-8)). SNPs in both regions were associated in over 20,000 individuals and are supported by prior associations or functional evidence. Four additional significant regions were detected in secondary sex-stratified and combined discovery and replication analyses, including a region overlapping Reelin, a known marker of respiratory complex neurons.These are the first genome-wide significant findings reported for oxyhemoglobin saturation during sleep, a phenotype of high clinical interest. Our replicated associations with HK1 and IL18R1 suggest that variants in inflammatory pathways, such as the biologically-plausible NLRP3 inflammasome, may contribute to nocturnal hypoxemia.
Indexed as
AdolescentAdultAgedAged, 80 and overCell Adhesion Molecules, NeuronalComputational BiologyExtracellular Matrix ProteinsFemaleGene Regulatory NetworksGenetic VariationGenome-Wide Association StudyHexokinaseHumansHypoxiaInterleukin-18 Receptor alpha SubunitMaleCell Adhesion Molecules, NeuronalExtracellular Matrix ProteinsHexokinaseHK1 protein, humanIL18R1 protein, humanInterleukin-18 Receptor alpha SubunitNerve Tissue ProteinsNLR Family, Pyrin Domain-Containing 3 ProteinNLRP3 protein, humanOxygenOxyhemoglobinsReelin ProteinRELN protein, humanSerine Endopeptidases
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