Genome-wide association study identifies human genetic variants associated with fatal outcome from Lassa fever.

Autor:	Kotliar D; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA. dkotliar@mgb.org.; Department of Systems Biology, Harvard Medical School, Boston, MA, USA. dkotliar@mgb.org.; Department of Internal Medicine, Brigham and Women's Hospital, Boston, MA, USA. dkotliar@mgb.org., Raju S; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.; Department of Systems Biology, Harvard Medical School, Boston, MA, USA., Tabrizi S; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.; Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, USA.; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA., Odia I; Institute of Lassa Fever, Research and Control, Irrua Specialist Teaching Hospital, Irrua, Nigeria., Goba A; College of Medicine and Allied Health Sciences, University of Sierra Leone, Freetown, Sierra Leone., Momoh M; College of Medicine and Allied Health Sciences, University of Sierra Leone, Freetown, Sierra Leone.; Eastern Polytechnic College, Kenema, Sierra Leone., Sandi JD; College of Medicine and Allied Health Sciences, University of Sierra Leone, Freetown, Sierra Leone., Nair P; Howard Hughes Medical Institute, Chevy Chase, MD, USA., Phelan E; Prospr at Work Inc., Berlin, Germany., Tariyal R; NextGen Jane, Inc., Oakland, CA, USA., Eromon PE; Institute of Lassa Fever, Research and Control, Irrua Specialist Teaching Hospital, Irrua, Nigeria.; African Centre of Excellence for Genomics of Infectious Diseases (ACEGID), Redeemer's University, Ede, Nigeria., Mehta S; Department of Critical Care Medicine, University of Maryland Medical Center, Baltimore, MA, USA., Robles-Sikisaka R; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA., Siddle KJ; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA., Stremlau M; Equator Labs Incorporated, Washington, DC, USA., Jalloh S; College of Medicine and Allied Health Sciences, University of Sierra Leone, Freetown, Sierra Leone., Gire SK; NextGen Jane, Inc., Oakland, CA, USA., Winnicki S; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA., Chak B; Biological Sciences Division, University of Chicago, Chicago, IL, USA., Schaffner SF; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.; Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA, USA.; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA., Pauthner M; Vir Biotechnology, San Francisco, CA, USA., Karlsson EK; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.; Genomics and Computational Biology, UMass Chan Medical School, Worcester, MA, USA.; Program in Molecular Medicine, UMass Chan Medical School, Worcester, MA, USA., Chapin SR; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA., Kennedy SG; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.; Department of Medicine, Massachusetts General Hospital, Boston, MA, USA., Branco LM; Zalgen Labs, Frederick, MD, USA., Kanneh L; Viral Hemorrhagic Fever Program, Kenema Government Hospital, Ministry of Health and Sanitation, Kenema, Sierra Leone., Vitti JJ; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA., Broodie N; New York-Presbyterian Hospital-Columbia and Cornell, New York, NY, USA., Gladden-Young A; Molecular Microbiology, Graduate School of Biomedical Sciences, Tufts University, Boston, MA, USA., Omoniwa O; Malaria Consortium, Abuja, Nigeria., Jiang PP; Google Medical Brain, Mountain View, CA, USA., Yozwiak N; Gene and Cell Therapy Institute, Mass General Brigham, Cambridge, MA, USA., Heuklom S; San Francisco Community Health Center, San Francisco, CA, USA., Moses LM; Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA., Akpede GO; Institute of Lassa Fever, Research and Control, Irrua Specialist Teaching Hospital, Irrua, Nigeria.; Department of Medicine, Ambrose Alli University, Ekpoma, Nigeria., Asogun DA; Department of Community Medicine, Ambrose Alli University, Ekpoma, Nigeria., Rubins K; National Aeronautics and Space Administration, Houston, TX, USA., Kales S; The Jackson Laboratory, Bar Harbor, ME, USA., Happi AN; African Centre of Excellence for Genomics of Infectious Diseases (ACEGID), Redeemer's University, Ede, Nigeria., Iruolagbe CO; Department of Medicine, Irrua Specialist Teaching Hospital, Irrua, Nigeria., Dic-Ijiewere M; Department of Medicine, Irrua Specialist Teaching Hospital, Irrua, Nigeria., Iraoyah K; Department of Medicine, Irrua Specialist Teaching Hospital, Irrua, Nigeria., Osazuwa OO; Department of Medicine, Irrua Specialist Teaching Hospital, Irrua, Nigeria., Okonkwo AK; Department of Medicine, Irrua Specialist Teaching Hospital, Irrua, Nigeria., Kunz S; Institute of Microbiology, University Hospital Center and University of Lausanne, Lausanne, Switzerland., McCormick JB; UTHealth Houston School of Public Health, Brownsville Campus, Brownsville, TX, USA., Khan SH; College of Medicine and Allied Health Sciences, University of Sierra Leone, Freetown, Sierra Leone., Honko AN; Boston University School of Medicine, Boston, MA, USA., Lander ES; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.; Department of Systems Biology, Harvard Medical School, Boston, MA, USA.; Department of Biology, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA., Oldstone MBA; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA., Hensley L; National Institutes of Health Integrated Research Facility, Frederick, MA, USA., Folarin OA; African Centre of Excellence for Genomics of Infectious Diseases (ACEGID), Redeemer's University, Ede, Nigeria.; Department of Biological Sciences, Redeemer's University, Ede, Nigeria., Okogbenin SA; Institute of Lassa Fever, Research and Control, Irrua Specialist Teaching Hospital, Irrua, Nigeria., Günther S; Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany., Ollila HM; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.; Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.; Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Tewhey R; The Jackson Laboratory, Bar Harbor, ME, USA., Okokhere PO; Institute of Lassa Fever, Research and Control, Irrua Specialist Teaching Hospital, Irrua, Nigeria.; Department of Medicine, Ambrose Alli University, Ekpoma, Nigeria.; Department of Medicine, Irrua Specialist Teaching Hospital, Irrua, Nigeria., Schieffelin JS; Section of Infectious Disease, Department of Pediatrics, Tulane University School of Medicine, New Orleans, LA, USA., Andersen KG; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA., Reilly SK; Department of Genetics, Yale School of Medicine, New Haven, CT, USA., Grant DS; College of Medicine and Allied Health Sciences, University of Sierra Leone, Freetown, Sierra Leone.; Viral Hemorrhagic Fever Program, Kenema Government Hospital, Ministry of Health and Sanitation, Kenema, Sierra Leone., Garry RF; Tulane University School of Medicine, New Orleans, LA, USA., Barnes KG; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA.; Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Kamuzu University of Health Sciences, Blantyre, Malawi.; Department of Vector Biology and Tropical Disease Biology, Liverpool School of Tropical Medicine, Liverpool, UK., Happi CT; African Centre of Excellence for Genomics of Infectious Diseases (ACEGID), Redeemer's University, Ede, Nigeria. happic@run.edu.ng.; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA. happic@run.edu.ng.; Department of Biological Sciences, Redeemer's University, Ede, Nigeria. happic@run.edu.ng., Sabeti PC; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA. pardis@broadinstitute.org.; Howard Hughes Medical Institute, Chevy Chase, MD, USA. pardis@broadinstitute.org.; Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA, USA. pardis@broadinstitute.org.; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA. pardis@broadinstitute.org.; Department of Medicine, Massachusetts General Hospital, Boston, MA, USA. pardis@broadinstitute.org.; Massachusetts Consortium on Pathogen Readiness, Boston, MA, USA. pardis@broadinstitute.org.
Jazyk:	angličtina
Zdroj:	Nature microbiology [Nat Microbiol] 2024 Mar; Vol. 9 (3), pp. 751-762. Date of Electronic Publication: 2024 Feb 07.
DOI:	10.1038/s41564-023-01589-3
Abstrakt:	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. (© 2024. The Author(s).)
Databáze:	MEDLINE
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