Genetic regulation of OAS1 nonsense-mediated decay underlies association with COVID-19 hospitalization in patients of European and African ancestries.

Autor: 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.; Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, FL, USA., Florez-Vargas O; Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, 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; Toronto Centre for Liver Disease, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada., Mirabello L; Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA., Ring TJ; Laboratory of Translational Genomics, 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; Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA., Andreakos E; Laboratory of Immunobiology, Center for Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece., Arons E; Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA., Barsh G; HudsonAlpha Institute for Biotechnology, Huntsville, AL, USA., Biesecker LG; Center for Precision Health Research, National Human Genome Research Institute, Bethesda, MD, USA., Boyle DL; Altman Clinical & Translational Research Institute, UC San Diego Health Sciences, San Diego, CA, USA., Brahier MS; Georgetown University School of Medicine, Washington, DC, USA., Burnett-Hartman A; Institute for Health Research, Kaiser Permanente Colorado, Aurora, CO, USA., Carrington M; Basic Science Program, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, MD, USA.; Laboratory of Integrative Cancer Immunology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA., Chang E; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea., Choe PG; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea., Chisholm RL; Center for Genetic Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA., Colli LM; Department of Medical Imaging, Hematology, and Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Dalgard CL; Uniformed Services University of the Health Sciences, Bethesda, MD, USA., Dude CM; Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, GA, USA., Edberg J; Department of Medicine, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL, USA., Erdmann N; Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, AL, USA., Feigelson HS; Institute for Health Research, Kaiser Permanente Colorado, Aurora, CO, USA., Fonseca BA; Department of Internal Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Firestein GS; Altman Clinical & Translational Research Institute, UC San Diego Health Sciences, San Diego, CA, USA., Gehring AJ; Toronto Centre for Liver Disease, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada.; Department of Immunology, University of Toronto, Toronto, Ontario, Canada., Guo C; Division of Cellular Polarity and Viral Infection, German Cancer Research Center (DKFZ), Heidelberg, Germany., Ho M; Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA., Holland S; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA., Hutchinson AA; Cancer Genomics Research Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD, USA., Im H; Genome Opinion, Inc., Seoul, Republic of Korea., Irby L; Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, GA, USA., Ison MG; Divisions of Infectious Diseases and Organ Transplantation, Northwestern University Feinberg School of Medicine, Chicago, IL, USA., Joseph NT; Department of Obstetrics & Gynecology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA., Kim HB; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.; Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea., Kreitman RJ; Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA., Korf BR; Department of Genetics, University of Alabama at Birmingham, Birmingham, AL, USA., Lipkin SM; Department of Medicine and Program in Mendelian Genetics, Weill Cornell Medicine, New York, NY, USA., Mahgoub SM; Department of Medicine, Infectious Diseases Division, Howard University Hospital, Howard University College of Medicine, Washington, DC, USA., Mohammed I; Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA., Paschoalini GL; Department of Medical Imaging, Hematology, and Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Pacheco JA; Center for Genetic Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA., Peluso MJ; Division of HIV, Infectious Diseases and Global Medicine, University of California, San Francisco, CA, USA., Rader DJ; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Redden DT; Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA., Ritchie MD; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Rosenblum B; Center for Precision Health Research, National Human Genome Research Institute, Bethesda, MD, USA., Ross ME; Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA., Anna HPS; Laboratory of Genetic Susceptibility, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA., Savage SA; Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA., Sharma S; Department of Biochemistry and Molecular Biology, National Human Genome Center, Howard University College of Medicine, Washington, DC, USA., Siouti E; Laboratory of Immunobiology, Center for Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece., Smith AK; Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, GA, USA., Triantafyllia V; Laboratory of Immunobiology, Center for Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece., Vargas JM; Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA., Vargas JD; Veterans Affairs Medical Center, Washington, DC, USA., Verma A; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Vij V; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA., Wesemann DR; Department of Medicine, Division of Allergy and Immunology, Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Yeager M; Cancer Genomics Research Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD, USA., Yu X; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA., Zhang Y; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA., Boulant S; Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, FL, USA.; Division of Cellular Polarity and Viral Infection, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Department of Infectious Diseases, Virology, University Hospital Heidelberg, Heidelberg, Germany., Chanock SJ; Laboratory of Genetic Susceptibility, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA., Feld JJ; Toronto Centre for Liver Disease, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada.; Department of Immunology, University of Toronto, Toronto, Ontario, Canada., Prokunina-Olsson L; Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA. prokuninal@mail.nih.gov.
Jazyk: angličtina
Zdroj: Nature genetics [Nat Genet] 2022 Aug; Vol. 54 (8), pp. 1103-1116. Date of Electronic Publication: 2022 Jul 14.
DOI: 10.1038/s41588-022-01113-z
Abstrakt: 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.
(© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
Databáze: MEDLINE
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