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Multiethnic Meta-Analysis Identifies RAI1 as a Possible Obstructive Sleep Apnea-related Quantitative Trait Locus in Men.

  • Chen H 1 Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
  • Cade BE 4 Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, Massachusetts.
  • Gleason KJ 4 Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, Massachusetts.
  • Bjonnes AC 7 Division of Genetics, Brigham and Women's Hospital, Boston, Massachusetts.
  • Stilp AM 9 Department of Biostatistics, University of Washington, Seattle, Washington.
  • Sofer T 4 Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, Massachusetts.
  • Conomos MP 9 Department of Biostatistics, University of Washington, Seattle, Washington.
  • Ancoli-Israel S 10 Departments of Medicine and Psychiatry, University of California, San Diego, California.
  • Arens R 11 the Children's Hospital at Montefiore, Division of Respiratory and Sleep Medicine, Albert Einstein College of Medicine, Bronx, New York.
  • Azarbarzin A 4 Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, Massachusetts.
  • Bell GI 12 Section of Adult and Pediatric Endocrinology, Diabetes, and Metabolism, the University of Chicago, Chicago, Illinois.
  • Below JE 2 Human Genetics Center, Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health and.
  • Chun S 7 Division of Genetics, Brigham and Women's Hospital, Boston, Massachusetts.
  • Evans DS 15 California Pacific Medical Center Research Institute, San Francisco, California.
  • Ewert R 16 Internal Medicine B, University Medicine Greifswald, Greifswald, Germany.
  • Frazier-Wood AC 17 Children's Nutrition Research Center, Baylor College of Medicine, Houston, Texas.
  • Gharib SA 18 Computational Medicine Core, Center for Lung Biology, University of Washington Medicine Sleep Center, Division of Pulmonary, Critical Care, and Sleep Medicine, University of Washington, Seattle, Washington.
  • Haba-Rubio J 19 Center of Investigation and Research on Sleep, Lausanne University Hospital, Lausanne, Switzerland.
  • Hagen EW 20 Department of Population Health Sciences, University of Wisconsin, Madison, Wisconsin.
  • Heinzer R 19 Center of Investigation and Research on Sleep, Lausanne University Hospital, Lausanne, Switzerland.
  • Hillman DR 21 Department of Pulmonary Physiology and Sleep Medicine, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia.
  • Johnson WC 9 Department of Biostatistics, University of Washington, Seattle, Washington.
  • Kutalik Z 22 Institute of Social and Preventive Medicine, University Hospital of Lausanne, Lausanne, Switzerland.
  • Lane JM 4 Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, Massachusetts.
  • Larkin EK 25 Department of Medicine, Division of Allergy, Pulmonary, and Critical Care, Vanderbilt University Medical Center, Nashville, Tennessee.
  • Lee SK 26 Institute of Human Genomic Study, College of Medicine, Korea University Ansan Hospital, Jeokgum-ro, Danwon-gu, Ansan-si, Gyeonggi-Do, Republic of Korea.
  • Liang J 27 Department of Epidemiology and Biostatistics, School of Medicine, Case Western Reserve University, Cleveland, Ohio.
  • Loredo JS 28 Division of Pulmonary Critical Care and Sleep Medicine, Department of Medicine, University of California San Diego School of Medicine, La Jolla, California.
  • Mukherjee S 29 Adelaide Institute for Sleep Health, Flinders Centre of Research Excellence, Flinders University, Adelaide, South Australia, Australia.
  • Palmer LJ 30 School of Public Health, University of Adelaide, Adelaide, South Australia, Australia.
  • Papanicolaou GJ 31 Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, Bethesda, Maryland.
  • Penzel T 32 University Hospital Charité Berlin, Sleep Center, Berlin, Germany.
  • Peppard PE 20 Department of Population Health Sciences, University of Wisconsin, Madison, Wisconsin.
  • Post WS 33 Division of Cardiology, Johns Hopkins University, Baltimore, Maryland.
  • Ramos AR 34 Department of Neurology, University of Miami Miller School of Medicine, Miami, Florida.
  • Rice K 9 Department of Biostatistics, University of Washington, Seattle, Washington.
  • Rotter JI 35 Institute for Translational Genomics and Population Sciences, Los Angeles BioMedical Research Institute and Department of Pediatrics at Harbor-University of California Los Angeles Medical Center, Torrance, California.
  • Sands SA 4 Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, Massachusetts.
  • Shah NA 36 Division of Pulmonary, Critical Care, and Sleep, Icahn School of Medicine at Mount Sinai, New York, New York.
  • Shin C 37 Department of Pulmonary, Sleep, and Critical Care Medicine, College of Medicine, Korea University Ansan Hospital, Jeokgum-ro, Danwon-gu, Ansan-si, Gyeonggi-do, Republic of Korea.
  • Stone KL 15 California Pacific Medical Center Research Institute, San Francisco, California.
  • Stubbe B 16 Internal Medicine B, University Medicine Greifswald, Greifswald, Germany.
  • Sul JH 7 Division of Genetics, Brigham and Women's Hospital, Boston, Massachusetts.
  • Tafti M 19 Center of Investigation and Research on Sleep, Lausanne University Hospital, Lausanne, Switzerland.
  • Taylor KD 35 Institute for Translational Genomics and Population Sciences, Los Angeles BioMedical Research Institute and Department of Pediatrics at Harbor-University of California Los Angeles Medical Center, Torrance, California.
  • Teumer A 40 Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
  • Thornton TA 9 Department of Biostatistics, University of Washington, Seattle, Washington.
  • Tranah GJ 15 California Pacific Medical Center Research Institute, San Francisco, California.
  • Wang C 1 Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
  • Wang H 4 Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, Massachusetts.
  • Warby SC 42 Department of Psychiatry, University of Montreal, Montreal, Quebec, Canada.
  • Wellman DA 4 Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, Massachusetts.
  • Zee PC 43 Department of Neurology and Sleep Medicine Center, Northwestern University, Chicago, Illinois.
  • Hanis CL 2 Human Genetics Center, Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health and.
  • Laurie CC 9 Department of Biostatistics, University of Washington, Seattle, Washington.
  • Gottlieb DJ 4 Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, Massachusetts.
  • Patel SR 45 Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
  • Zhu X 27 Department of Epidemiology and Biostatistics, School of Medicine, Case Western Reserve University, Cleveland, Ohio.
  • Sunyaev SR 7 Division of Genetics, Brigham and Women's Hospital, Boston, Massachusetts.
  • Saxena R 4 Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, Massachusetts.
  • Lin X 1 Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
  • Redline S 4 Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, Massachusetts.
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  • 2017-10-28
Published in:
  • American journal of respiratory cell and molecular biology. - 2018
genetics
genome-wide association studies
multiethnic
obstructive sleep apnea
sexual dimorphism
Adult
Aged
Female
Genome-Wide Association Study
Humans
Male
Middle Aged
Phosphatidylethanolamine N-Methyltransferase
Quantitative Trait Loci
Sex Characteristics
Sleep Apnea, Obstructive
Sleep, REM
Sterol Regulatory Element Binding Protein 1
Transcription Factors
ras Proteins
English Obstructive sleep apnea (OSA) is a common heritable disorder displaying marked sexual dimorphism in disease prevalence and progression. Previous genetic association studies have identified a few genetic loci associated with OSA and related quantitative traits, but they have only focused on single ethnic groups, and a large proportion of the heritability remains unexplained. The apnea-hypopnea index (AHI) is a commonly used quantitative measure characterizing OSA severity. Because OSA differs by sex, and the pathophysiology of obstructive events differ in rapid eye movement (REM) and non-REM (NREM) sleep, we hypothesized that additional genetic association signals would be identified by analyzing the NREM/REM-specific AHI and by conducting sex-specific analyses in multiethnic samples. We performed genome-wide association tests for up to 19,733 participants of African, Asian, European, and Hispanic/Latino American ancestry in 7 studies. We identified rs12936587 on chromosome 17 as a possible quantitative trait locus for NREM AHI in men (N = 6,737; P = 1.7 × 10-8) but not in women (P = 0.77). The association with NREM AHI was replicated in a physiological research study (N = 67; P = 0.047). This locus overlapping the RAI1 gene and encompassing genes PEMT1, SREBF1, and RASD1 was previously reported to be associated with coronary artery disease, lipid metabolism, and implicated in Potocki-Lupski syndrome and Smith-Magenis syndrome, which are characterized by abnormal sleep phenotypes. We also identified gene-by-sex interactions in suggestive association regions, suggesting that genetic variants for AHI appear to vary by sex, consistent with the clinical observations of strong sexual dimorphism.
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  • English
Open access status
green
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https://sonar.ch/global/documents/106255
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