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Genetic regulation of OAS1 nonsense-mediated decay underlies association with COVID-19 hospitalization in patients of European and African ancestries.
Banday, A Rouf; Stanifer, Megan L; Florez-Vargas, Oscar; Onabajo, Olusegun O; Papenberg, Brenen W; Zahoor, Muhammad A; Mirabello, Lisa; Ring, Timothy J; Lee, Chia-Han; Albert, Paul S; Andreakos, Evangelos; Arons, Evgeny; Barsh, Greg; Biesecker, Leslie G; Boyle, David L; Brahier, Mark S; Burnett-Hartman, Andrea; Carrington, Mary; Chang, Euijin; Choe, Pyoeng Gyun; Chisholm, Rex L; Colli, Leandro M; Dalgard, Clifton L; Dude, Carolynn M; Edberg, Jeff; Erdmann, Nathan; Feigelson, Heather S; Fonseca, Benedito A; Firestein, Gary S; Gehring, Adam J; Guo, Cuncai; Ho, Michelle; Holland, Steven; Hutchinson, Amy A; Im, Hogune; Irby, Les'Shon; Ison, Michael G; Joseph, Naima T; Kim, Hong Bin; Kreitman, Robert J; Korf, Bruce R; Lipkin, Steven M; Mahgoub, Siham M; Mohammed, Iman; Paschoalini, Guilherme L; Pacheco, Jennifer A; Peluso, Michael J; Rader, Daniel J; Redden, David T; Ritchie, Marylyn D.
  • Banday AR; Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
  • Stanifer ML; Department of Infectious Diseases, Molecular Virology, University Hospital Heidelberg, Heidelberg, Germany.
  • Florez-Vargas O; Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, FL, USA.
  • Onabajo OO; Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
  • Papenberg BW; Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
  • Zahoor MA; Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
  • Mirabello L; Toronto Centre for Liver Disease, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada.
  • Ring TJ; Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
  • Lee CH; Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
  • Albert PS; Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
  • Andreakos E; Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
  • Arons E; Laboratory of Immunobiology, Center for Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
  • Barsh G; Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
  • Biesecker LG; HudsonAlpha Institute for Biotechnology, Huntsville, AL, USA.
  • Boyle DL; Center for Precision Health Research, National Human Genome Research Institute, Bethesda, MD, USA.
  • Brahier MS; Altman Clinical & Translational Research Institute, UC San Diego Health Sciences, San Diego, CA, USA.
  • Burnett-Hartman A; Georgetown University School of Medicine, Washington, DC, USA.
  • Carrington M; Institute for Health Research, Kaiser Permanente Colorado, Aurora, CO, USA.
  • Chang E; Basic Science Program, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, MD, USA.
  • Choe PG; Laboratory of Integrative Cancer Immunology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
  • Chisholm RL; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
  • Colli LM; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
  • Dalgard CL; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
  • Dude CM; Center for Genetic Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
  • Edberg J; Department of Medical Imaging, Hematology, and Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
  • Erdmann N; Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
  • Feigelson HS; Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, GA, USA.
  • Fonseca BA; Department of Medicine, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL, USA.
  • Firestein GS; Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, AL, USA.
  • Gehring AJ; Institute for Health Research, Kaiser Permanente Colorado, Aurora, CO, USA.
  • Guo C; Department of Internal Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
  • Ho M; Altman Clinical & Translational Research Institute, UC San Diego Health Sciences, San Diego, CA, USA.
  • Holland S; Toronto Centre for Liver Disease, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada.
  • Hutchinson AA; Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
  • Im H; Division of Cellular Polarity and Viral Infection, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Irby L; Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
  • Ison MG; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA.
  • Joseph NT; Cancer Genomics Research Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
  • Kim HB; Genome Opinion, Inc., Seoul, Republic of Korea.
  • Kreitman RJ; Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, GA, USA.
  • Korf BR; Divisions of Infectious Diseases and Organ Transplantation, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
  • Lipkin SM; Department of Obstetrics & Gynecology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
  • Mahgoub SM; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
  • Mohammed I; Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
  • Paschoalini GL; Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
  • Pacheco JA; Department of Genetics, University of Alabama at Birmingham, Birmingham, AL, USA.
  • Peluso MJ; Department of Medicine and Program in Mendelian Genetics, Weill Cornell Medicine, New York, NY, USA.
  • Rader DJ; Department of Medicine, Infectious Diseases Division, Howard University Hospital, Howard University College of Medicine, Washington, DC, USA.
  • Redden DT; Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.
  • Ritchie MD; Department of Medical Imaging, Hematology, and Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
Nat Genet ; 54(8): 1103-1116, 2022 08.
Article in English | MEDLINE | ID: covidwho-1931425
ABSTRACT
The chr12q24.13 locus encoding OAS1-OAS3 antiviral proteins has been associated with coronavirus disease 2019 (COVID-19) susceptibility. Here, we report genetic, functional and clinical insights into this locus in relation to COVID-19 severity. In our analysis of patients of European (n = 2,249) and African (n = 835) ancestries with hospitalized versus nonhospitalized COVID-19, the risk of hospitalized disease was associated with a common OAS1 haplotype, which was also associated with reduced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) clearance in a clinical trial with pegIFN-λ1. Bioinformatic analyses and in vitro studies reveal the functional contribution of two associated OAS1 exonic variants comprising the risk haplotype. Derived human-specific alleles rs10774671-A and rs1131454 -A decrease OAS1 protein abundance through allele-specific regulation of splicing and nonsense-mediated decay (NMD). We conclude that decreased OAS1 expression due to a common haplotype contributes to COVID-19 severity. Our results provide insight into molecular mechanisms through which early treatment with interferons could accelerate SARS-CoV-2 clearance and mitigate against severe COVID-19.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Type of study: Prognostic study / Randomized controlled trials Topics: Variants Limits: Humans Language: English Journal: Nat Genet Journal subject: Genetics, Medical Year: 2022 Document Type: Article Affiliation country: S41588-022-01113-z

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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Type of study: Prognostic study / Randomized controlled trials Topics: Variants Limits: Humans Language: English Journal: Nat Genet Journal subject: Genetics, Medical Year: 2022 Document Type: Article Affiliation country: S41588-022-01113-z