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Genetic and non-genetic factors affecting the expression of COVID-19 relevant genes in the large airway epithelium
Silva Kasela; Victor E Ortega; Molly Martorella; Suresh Garudadri; Jenna Nguyen; Elizabeth Ampleford; Anu Pasanen; Srilaxmi Nerella; Kristina L Buschur; Igor Z Barjaktarevic; R Graham Barr; Eugene R Bleecker; Russell P Bowler; Alejandro P Comellas; Christopher B Cooper; David J Couper; Gerard J Criner; Jeffrey L Curtis; MeiLan K Han; Nadia N Hansel; Eric A Hoffman; Robert J Kaner; Jerry A Krishnan; Fernando J Martinez; Merry-Lynn N McDonald; Deborah A Meyers; Robert Paine III; Stephen P Peters; Mario Castro; Loren C Denlinger; Serpil C Erzurum; John V Fahy; Elliot Israel; Nizar N Jarjour; Bruce D Levy; Xingnan Li; Wendy C Moore; Sally E Wenzel; Joe Zein; - NHLBI SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS); - NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium; Charles Langelier; Prescott G Woodruff; Tuuli Lappalainen; Stephanie A Christenson.
Afiliação
  • Silva Kasela; New York Genome Center, New York, NY, USA; Department of Systems Biology, Columbia University, New York, NY, USA
  • Victor E Ortega; Department of Internal Medicine, Section of Pulmonary, Critical Care, Allergy and Immunologic Diseases, Wake Forest School of Medicine, Winston-Salem, NC, USA
  • Molly Martorella; New York Genome Center, New York, NY, USA; Department of Systems Biology, Columbia University, New York, NY, USA
  • Suresh Garudadri; Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA
  • Jenna Nguyen; Division of Pulmonary, Critical Care, Allergy, & Sleep Medicine, Department of Medicine, University of California San Francisco, San Francisco, CA, USA
  • Elizabeth Ampleford; Department of Internal Medicine, Section of Pulmonary, Critical Care, Allergy and Immunologic Diseases, Wake Forest School of Medicine, Winston-Salem, NC, USA
  • Anu Pasanen; New York Genome Center, New York, NY, USA; Department of Systems Biology, Columbia University, New York, NY, USA
  • Srilaxmi Nerella; Division of Pulmonary, Critical Care, Allergy, & Sleep Medicine, Department of Medicine, University of California San Francisco, San Francisco, CA, USA
  • Kristina L Buschur; New York Genome Center, New York, NY, USA; Department of Medicine, Columbia University Medical Center, New York, NY, USA
  • Igor Z Barjaktarevic; Division of Pulmonary and Critical Care Medicine, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA
  • R Graham Barr; Department of Medicine, Columbia University Medical Center, New York, NY, USA
  • Eugene R Bleecker; Division of Genetics, Genomics and Precision Medicine, Department of Medicine, University of Arizona, Tucson, AZ, USA
  • Russell P Bowler; Division of Pulmonary Medicine, Department of Medicine, National Jewish Health, Denver, CO, USA
  • Alejandro P Comellas; Division of Pulmonary and Critical Care, University of Iowa, Iowa City, IA, USA
  • Christopher B Cooper; Division of Pulmonary and Critical Care Medicine, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA
  • David J Couper; Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
  • Gerard J Criner; Department of Thoracic Medicine and Surgery, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA
  • Jeffrey L Curtis; Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Michigan Health System, Ann Arbor, MI, USA; Medicine Service, VA Ann Arb
  • MeiLan K Han; Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Michigan Health System, Ann Arbor, MI, USA
  • Nadia N Hansel; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA
  • Eric A Hoffman; Division of Physiologic Imaging, Department of Radiology, University of Iowa Hospitals and Clinics, Iowa City, IA, USA
  • Robert J Kaner; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Weill Cornell Medicine, New York, NY, USA; Department of Genetic Medicine, We
  • Jerry A Krishnan; Division of Pulmonary, Critical Care, Sleep and Allergy, University of Illinois at Chicago, Chicago, IL, USA
  • Fernando J Martinez; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Weill Cornell Medicine, New York, NY, USA
  • Merry-Lynn N McDonald; Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
  • Deborah A Meyers; Division of Genetics, Genomics and Precision Medicine, Department of Medicine, University of Arizona, Tucson, AZ, USA
  • Robert Paine III; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA
  • Stephen P Peters; Department of Internal Medicine, Section of Pulmonary, Critical Care, Allergy and Immunologic Diseases, Wake Forest School of Medicine, Winston-Salem, NC, USA
  • Mario Castro; Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, University of Kansas School of Medicine, Kansas City, KS, USA
  • Loren C Denlinger; Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, University of Wisconsin-Madison, Madison, WI, USA
  • Serpil C Erzurum; Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
  • John V Fahy; Division of Pulmonary, Critical Care, Allergy, & Sleep Medicine, Department of Medicine, University of California San Francisco, San Francisco, CA, USA
  • Elliot Israel; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA
  • Nizar N Jarjour; Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, University of Wisconsin-Madison, Madison, WI, USA
  • Bruce D Levy; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA
  • Xingnan Li; Division of Genetics, Genomics and Precision Medicine, Department of Medicine, University of Arizona, Tucson, AZ, USA
  • Wendy C Moore; Department of Internal Medicine, Section of Pulmonary, Critical Care, Allergy and Immunologic Diseases, Wake Forest School of Medicine, Winston-Salem, NC, USA
  • Sally E Wenzel; Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
  • Joe Zein; Respiratory Institute, Cleveland Clinic, Cleveland, OH, USA
  • - NHLBI SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS);
  • - NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium;
  • Charles Langelier; Division of Infectious Diseases, University of California San Francisco, San Francisco, CA, USA; Chan Zuckerberg Biohub, San Francisco, CA, USA
  • Prescott G Woodruff; Division of Pulmonary, Critical Care, Allergy, & Sleep Medicine, Department of Medicine, University of California San Francisco, San Francisco, CA, USA
  • Tuuli Lappalainen; New York Genome Center, New York, NY, USA; Department of Systems Biology, Columbia University, New York, NY, USA
  • Stephanie A Christenson; Division of Pulmonary, Critical Care, Allergy, & Sleep Medicine, Department of Medicine, University of California San Francisco, San Francisco, CA, USA
Preprint em Inglês | medRxiv | ID: ppmedrxiv-20202820
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ABSTRACT
Introductory paragraphParticular host and environmental factors influence susceptibility to severe COVID-19. We analyzed RNA-sequencing data from bronchial epithelial brushings - a relevant tissue for SARS-CoV-2 infection - obtained from three cohorts of uninfected individuals, and investigated how non-genetic and genetic factors affect the regulation of host genes implicated in COVID-19. We found that ACE2 expression was higher in relation to active smoking, obesity, and hypertension that are known risk factors of COVID-19 severity, while an association with interferon-related inflammation was driven by the truncated, non-binding ACE2 isoform. We discovered that expression patterns of a suppressed airway immune response to early SARS-CoV-2 infection, compared to other viruses, are similar to patterns associated with obesity, hypertension, and cardiovascular disease, which may thus contribute to a COVID-19-susceptible airway environment. eQTL mapping identified regulatory variants for genes implicated in COVID-19, some of which had pheWAS evidence for their potential role in respiratory infections. These data provide evidence that clinically relevant variation in the expression of COVID-19-related genes is associated with host factors, environmental exposures, and likely host genetic variation.
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Texto completo: Disponível Coleções: Preprints Base de dados: medRxiv Tipo de estudo: Cohort_studies / Estudo observacional / Estudo prognóstico Idioma: Inglês Ano de publicação: 2020 Tipo de documento: Preprint
Texto completo
Adicionar na Minha BVS
Imprimir
XML
Buscar no Google
Texto completo: Disponível Coleções: Preprints Base de dados: medRxiv Tipo de estudo: Cohort_studies / Estudo observacional / Estudo prognóstico Idioma: Inglês Ano de publicação: 2020 Tipo de documento: Preprint