title: Genetic Associations with Obstructive Sleep Apnea Traits in Hispanic/Latino Americans.
abstract: BACKGROUND
  Obstructive sleep apnea is a common disorder associated with increased risk for cardiovascular disease, diabetes, and premature mortality. Although there is strong clinical and epidemiologic evidence supporting the importance of genetic factors in influencing obstructive sleep apnea, its genetic basis is still largely unknown. Prior genetic studies focused on traits defined using the apnea-hypopnea index, which contains limited information on potentially important genetically determined physiologic factors, such as propensity for hypoxemia and respiratory arousability.
  
  
  OBJECTIVE
  To define novel obstructive sleep apnea genetic risk loci for obstructive sleep apnea, we conducted genome-wide association studies of quantitative traits in Hispanic/Latino Americans from three cohorts.
  
  
  METHODS
  Genome-wide data from as many as 12,558 participants in the Hispanic Community Health Study/Study of Latinos, Multi-Ethnic Study of Atherosclerosis, and Starr County Health Studies population-based cohorts were metaanalyzed for association with the apnea-hypopnea index, average oxygen saturation during sleep, and average respiratory event duration.
  
  
  RESULTS
  Two novel loci were identified at genome-level significance (rs11691765, GPR83, P = 1.90 × 10-8for the apnea-hypopnea index, and rs35424364; C6ORF183/CCDC162P, P = 4.88 × 10-8for respiratory event duration) and seven additional loci were identified with suggestive significance (P < 5 × 10-7). Secondary sex-stratified analyses also identified one significant and several suggestive associations. Multiple loci overlapped genes with biologic plausibility.
  
  
  CONCLUSIONS
  These are the first genome-level significant findings reported for obstructive sleep apnea-related physiologic traits in any population. These findings identify novel associations in inflammatory, hypoxia signaling, and sleep pathways.
authors.affiliation: 1 Division of Sleep and Circadian Disorders and.|2 Division of Sleep Medicine and.
authors.forename: Brian E
authors.identifier: http://orcid.org/0000-0003-1424-0673
authors.initials: BE
authors.lastname: Cade
authors.affiliation: 3 Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
authors.forename: Han
authors.initials: H
authors.lastname: Chen
authors.affiliation: 4 Department of Biostatistics, University of Washington, Seattle, Washington.
authors.forename: Adrienne M
authors.initials: AM
authors.lastname: Stilp
authors.affiliation: 1 Division of Sleep and Circadian Disorders and.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Gleason
authors.affiliation: 4 Department of Biostatistics, University of Washington, Seattle, Washington.
authors.forename: Tamar
authors.initials: T
authors.lastname: Sofer
authors.affiliation: 5 Department of Medicine and.|6 Department of Psychiatry, University of California, San Diego, California.|7 Department of Veterans Affairs San Diego Center of Excellence for Stress and Mental Health, San Diego, California.
authors.forename: Sonia
authors.initials: S
authors.lastname: Ancoli-Israel
authors.affiliation: 8 The Children's Hospital at Montefiore, Division of Respiratory and Sleep Medicine, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Raanan
authors.initials: R
authors.lastname: Arens
authors.affiliation: 9 Section of Adult and Pediatric Endocrinology, Diabetes, and Metabolism, The University of Chicago, Chicago, Illinois.
authors.forename: Graeme I
authors.initials: GI
authors.lastname: Bell
authors.affiliation: 10 Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, Houston, Texas.
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Below
authors.affiliation: 11 Division of Genetics, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Bjonnes
authors.affiliation: 11 Division of Genetics, Brigham and Women's Hospital, Boston, Massachusetts.|12 Division of Medical Sciences, Harvard Medical School, Boston, Massachusetts.
authors.forename: Sung
authors.initials: S
authors.lastname: Chun
authors.affiliation: 4 Department of Biostatistics, University of Washington, Seattle, Washington.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Conomos
authors.affiliation: 13 California Pacific Medical Center Research Institute, San Francisco, California.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Evans
authors.affiliation: 4 Department of Biostatistics, University of Washington, Seattle, Washington.
authors.forename: W Craig
authors.initials: WC
authors.lastname: Johnson
authors.affiliation: 14 Children's Nutrition Research Center, Baylor College of Medicine, Houston, Texas.
authors.forename: Alexis C
authors.initials: AC
authors.lastname: Frazier-Wood
authors.affiliation: 1 Division of Sleep and Circadian Disorders and.|2 Division of Sleep Medicine and.|15 Center for Human Genetic Research and Department of Anesthesia, Pain, and Critical Care Medicine, Massachusetts General Hospital, Boston, Massachusetts.|16 Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts.
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Lane
authors.affiliation: 17 Department of Medicine, Division of Allergy, Pulmonary and Critical Care, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Emma K
authors.initials: EK
authors.lastname: Larkin
authors.affiliation: 18 Division of Pulmonary Critical Care and Sleep Medicine, Department of Medicine, UC San Diego School of Medicine, La Jolla, California.
authors.forename: Jose S
authors.initials: JS
authors.lastname: Loredo
authors.affiliation: 19 Division of Cardiology, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Wendy S
authors.initials: WS
authors.lastname: Post
authors.affiliation: 20 Department of Neurology, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Alberto R
authors.initials: AR
authors.lastname: Ramos
authors.affiliation: 4 Department of Biostatistics, University of Washington, Seattle, Washington.
authors.forename: Ken
authors.initials: K
authors.lastname: Rice
authors.affiliation: 21 Institute for Translational Genomics and Population Sciences, Los Angeles BioMedical Research Institute at Harbor-UCLA Medical Center, Torrance, California.
authors.forename: Jerome I
authors.initials: JI
authors.lastname: Rotter
authors.affiliation: 22 Department of Medicine, Montefiore Medical Center, Bronx, New York.
authors.forename: Neomi A
authors.initials: NA
authors.lastname: Shah
authors.affiliation: 13 California Pacific Medical Center Research Institute, San Francisco, California.
authors.forename: Katie L
authors.initials: KL
authors.lastname: Stone
authors.affiliation: 21 Institute for Translational Genomics and Population Sciences, Los Angeles BioMedical Research Institute at Harbor-UCLA Medical Center, Torrance, California.
authors.forename: Kent D
authors.initials: KD
authors.lastname: Taylor
authors.affiliation: 4 Department of Biostatistics, University of Washington, Seattle, Washington.
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Thornton
authors.affiliation: 13 California Pacific Medical Center Research Institute, San Francisco, California.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Tranah
authors.affiliation: 3 Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.|23 Genome Institute of Singapore, Singapore.
authors.forename: Chaolong
authors.initials: C
authors.lastname: Wang
authors.affiliation: 24 Department of Neurology and Sleep Medicine Center, Northwestern University, Chicago, Illinois.
authors.forename: Phyllis C
authors.initials: PC
authors.lastname: Zee
authors.affiliation: 10 Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, Houston, Texas.
authors.forename: Craig L
authors.initials: CL
authors.lastname: Hanis
authors.affiliation: 11 Division of Genetics, Brigham and Women's Hospital, Boston, Massachusetts.|12 Division of Medical Sciences, Harvard Medical School, Boston, Massachusetts.|16 Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts.
authors.forename: Shamil R
authors.initials: SR
authors.lastname: Sunyaev
authors.affiliation: 1 Division of Sleep and Circadian Disorders and.|2 Division of Sleep Medicine and.|25 Division of Pulmonary, Critical Care, and Sleep Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts; and.
authors.forename: Sanjay R
authors.initials: SR
authors.lastname: Patel
authors.affiliation: 4 Department of Biostatistics, University of Washington, Seattle, Washington.
authors.forename: Cathy C
authors.initials: CC
authors.lastname: Laurie
authors.affiliation: 26 Department of Epidemiology and Biostatistics, School of Medicine, Case Western Reserve University, Cleveland, Ohio.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Zhu
authors.affiliation: 1 Division of Sleep and Circadian Disorders and.|15 Center for Human Genetic Research and Department of Anesthesia, Pain, and Critical Care Medicine, Massachusetts General Hospital, Boston, Massachusetts.|16 Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts.
authors.forename: Richa
authors.initials: R
authors.lastname: Saxena
authors.affiliation: 3 Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
authors.forename: Xihong
authors.initials: X
authors.lastname: Lin
authors.affiliation: 1 Division of Sleep and Circadian Disorders and.|2 Division of Sleep Medicine and.|25 Division of Pulmonary, Critical Care, and Sleep Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts; and.
authors.forename: Susan
authors.initials: S
authors.lastname: Redline
keywords: GWAS; Prader–Willi syndrome; genetics; hypoxia; sleep apnea