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Genome-wide association study identifies human genetic variants associated with fatal outcome from Lassa fever.
Kotliar, Dylan; Raju, Siddharth; Tabrizi, Shervin; Odia, Ikponmwosa; Goba, Augustine; Momoh, Mambu; Sandi, John Demby; Nair, Parvathy; Phelan, Eric; Tariyal, Ridhi; Eromon, Philomena E; Mehta, Samar; Robles-Sikisaka, Refugio; Siddle, Katherine J; Stremlau, Matt; Jalloh, Simbirie; Gire, Stephen K; Winnicki, Sarah; Chak, Bridget; Schaffner, Stephen F; Pauthner, Matthias; Karlsson, Elinor K; Chapin, Sarah R; Kennedy, Sharon G; Branco, Luis M; Kanneh, Lansana; Vitti, Joseph J; Broodie, Nisha; Gladden-Young, Adrianne; Omoniwa, Omowunmi; Jiang, Pan-Pan; Yozwiak, Nathan; Heuklom, Shannon; Moses, Lina M; Akpede, George O; Asogun, Danny A; Rubins, Kathleen; Kales, Susan; Happi, Anise N; Iruolagbe, Christopher O; Dic-Ijiewere, Mercy; Iraoyah, Kelly; Osazuwa, Omoregie O; Okonkwo, Alexander K; Kunz, Stefan; McCormick, Joseph B; Khan, S Humarr; Honko, Anna N; Lander, Eric S; Oldstone, Michael B A.
Afiliação
  • Kotliar D; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA. dkotliar@mgb.org.
  • Raju S; Department of Systems Biology, Harvard Medical School, Boston, MA, USA. dkotliar@mgb.org.
  • Tabrizi S; Department of Internal Medicine, Brigham and Women's Hospital, Boston, MA, USA. dkotliar@mgb.org.
  • Odia I; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
  • Goba A; Department of Systems Biology, Harvard Medical School, Boston, MA, USA.
  • Momoh M; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
  • Sandi JD; Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, USA.
  • Nair P; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Phelan E; Institute of Lassa Fever, Research and Control, Irrua Specialist Teaching Hospital, Irrua, Nigeria.
  • Tariyal R; College of Medicine and Allied Health Sciences, University of Sierra Leone, Freetown, Sierra Leone.
  • Eromon PE; College of Medicine and Allied Health Sciences, University of Sierra Leone, Freetown, Sierra Leone.
  • Mehta S; Eastern Polytechnic College, Kenema, Sierra Leone.
  • Robles-Sikisaka R; College of Medicine and Allied Health Sciences, University of Sierra Leone, Freetown, Sierra Leone.
  • Siddle KJ; Howard Hughes Medical Institute, Chevy Chase, MD, USA.
  • Stremlau M; Prospr at Work Inc., Berlin, Germany.
  • Jalloh S; NextGen Jane, Inc., Oakland, CA, USA.
  • Gire SK; Institute of Lassa Fever, Research and Control, Irrua Specialist Teaching Hospital, Irrua, Nigeria.
  • Winnicki S; African Centre of Excellence for Genomics of Infectious Diseases (ACEGID), Redeemer's University, Ede, Nigeria.
  • Chak B; Department of Critical Care Medicine, University of Maryland Medical Center, Baltimore, MA, USA.
  • Schaffner SF; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
  • Pauthner M; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
  • Karlsson EK; Equator Labs Incorporated, Washington, DC, USA.
  • Chapin SR; College of Medicine and Allied Health Sciences, University of Sierra Leone, Freetown, Sierra Leone.
  • Kennedy SG; NextGen Jane, Inc., Oakland, CA, USA.
  • Branco LM; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
  • Kanneh L; Biological Sciences Division, University of Chicago, Chicago, IL, USA.
  • Vitti JJ; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
  • Broodie N; Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA, USA.
  • Gladden-Young A; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA.
  • Omoniwa O; Vir Biotechnology, San Francisco, CA, USA.
  • Jiang PP; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
  • Yozwiak N; Genomics and Computational Biology, UMass Chan Medical School, Worcester, MA, USA.
  • Heuklom S; Program in Molecular Medicine, UMass Chan Medical School, Worcester, MA, USA.
  • Moses LM; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
  • Akpede GO; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
  • Asogun DA; Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Rubins K; Zalgen Labs, Frederick, MD, USA.
  • Kales S; Viral Hemorrhagic Fever Program, Kenema Government Hospital, Ministry of Health and Sanitation, Kenema, Sierra Leone.
  • Happi AN; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
  • Iruolagbe CO; New York-Presbyterian Hospital-Columbia and Cornell, New York, NY, USA.
  • Dic-Ijiewere M; Molecular Microbiology, Graduate School of Biomedical Sciences, Tufts University, Boston, MA, USA.
  • Iraoyah K; Malaria Consortium, Abuja, Nigeria.
  • Osazuwa OO; Google Medical Brain, Mountain View, CA, USA.
  • Okonkwo AK; Gene and Cell Therapy Institute, Mass General Brigham, Cambridge, MA, USA.
  • Kunz S; San Francisco Community Health Center, San Francisco, CA, USA.
  • McCormick JB; Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA.
  • Khan SH; Institute of Lassa Fever, Research and Control, Irrua Specialist Teaching Hospital, Irrua, Nigeria.
  • Honko AN; Department of Medicine, Ambrose Alli University, Ekpoma, Nigeria.
  • Lander ES; Department of Community Medicine, Ambrose Alli University, Ekpoma, Nigeria.
  • Oldstone MBA; National Aeronautics and Space Administration, Houston, TX, USA.
Nat Microbiol ; 9(3): 751-762, 2024 Mar.
Article em En | MEDLINE | ID: mdl-38326571
ABSTRACT
Infection with Lassa virus (LASV) can cause Lassa fever, a haemorrhagic illness with an estimated fatality rate of 29.7%, but causes no or mild symptoms in many individuals. Here, to investigate whether human genetic variation underlies the heterogeneity of LASV infection, we carried out genome-wide association studies (GWAS) as well as seroprevalence surveys, human leukocyte antigen typing and high-throughput variant functional characterization assays. We analysed Lassa fever susceptibility and fatal outcomes in 533 cases of Lassa fever and 1,986 population controls recruited over a 7 year period in Nigeria and Sierra Leone. We detected genome-wide significant variant associations with Lassa fever fatal outcomes near GRM7 and LIF in the Nigerian cohort. We also show that a haplotype bearing signatures of positive selection and overlapping LARGE1, a required LASV entry factor, is associated with decreased risk of Lassa fever in the Nigerian cohort but not in the Sierra Leone cohort. Overall, we identified variants and genes that may impact the risk of severe Lassa fever, demonstrating how GWAS can provide insight into viral pathogenesis.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Febre Lassa Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: Nat Microbiol Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Febre Lassa Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: Nat Microbiol Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos