ArticleNature microbiology2024
Genome-wide association study identifies human genetic variants associated with fatal outcome from Lassa fever.
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Article in Nature microbiology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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8citing papers in PubMed
3.1field-weighted citation impact, top 9% of its field
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Who cites it
8 citing papers in PubMed, 8 citations in OpenAlex.
- Sequence to structure insights into Lassa virus population-level biophysical properties and glycoprotein structure catalogue.Npj viruses · 2026Article
- Mapping the scientific landscape of Lassa virus: a 55-year bibliometric study (1970-2025).Science in One Health · 2026Article
- The genetic basis of the immune response to SARS-CoV-2 infection and vaccination in the Italian municipality of Vo'.Frontiers in immunology · 2026Article
- CLASV: Rapid Lassa virus lineage assignment with random forest.PLoS neglected tropical diseases · 2025Article
- Lassa fever in African green monkeys: Clinical disease and fatal outcome are associated with systemic viral dissemination and inflammation.Cell reports. Medicine · 2025Article
- Unlocking the African bioeconomy and strengthening biodiversity conservation through genomics and bioinformatics.npj biodiversity · 2025Review
- Conference report of the 2024 Antimicrobial Resistance Meeting.npj antimicrobials and resistance · 2024Article
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Authors and funding
65 authors at 20 institutions in 8 countries.
Dylan Kotliar *Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA. dkotliar@mgb.org.ORCID http://orcid.org/0000-0002-7968-645X
Siddharth Raju *Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
Shervin Tabrizi *Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-2780-8432
Ikponmwosa Odia *Institute of Lassa Fever, Research and Control, Irrua Specialist Teaching Hospital, Irrua, Nigeria.
Augustine GobaCollege of Medicine and Allied Health Sciences, University of Sierra Leone, Freetown, Sierra Leone.
Mambu MomohCollege of Medicine and Allied Health Sciences, University of Sierra Leone, Freetown, Sierra Leone.ORCID http://orcid.org/0000-0001-7091-1027
John Demby SandiCollege of Medicine and Allied Health Sciences, University of Sierra Leone, Freetown, Sierra Leone.
Parvathy NairHoward Hughes Medical Institute, Chevy Chase, MD, USA.
Eric PhelanProspr at Work Inc., Berlin, Germany.
Ridhi TariyalNextGen Jane, Inc., Oakland, CA, USA.
Philomena E EromonInstitute of Lassa Fever, Research and Control, Irrua Specialist Teaching Hospital, Irrua, Nigeria.
Samar MehtaDepartment of Critical Care Medicine, University of Maryland Medical Center, Baltimore, MA, USA.
Refugio Robles-SikisakaDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
Katherine J SiddleBroad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-1799-7295
Matt StremlauEquator Labs Incorporated, Washington, DC, USA.
Simbirie JallohCollege of Medicine and Allied Health Sciences, University of Sierra Leone, Freetown, Sierra Leone.
Stephen K GireNextGen Jane, Inc., Oakland, CA, USA.ORCID http://orcid.org/0000-0002-7272-9728
Sarah WinnickiBroad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
Bridget ChakBiological Sciences Division, University of Chicago, Chicago, IL, USA.
Stephen F SchaffnerBroad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-6699-3568
Matthias PauthnerVir Biotechnology, San Francisco, CA, USA.ORCID http://orcid.org/0000-0001-9212-4307
Elinor K KarlssonBroad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-4343-3776
Sarah R ChapinBroad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-7775-3380
Sharon G KennedyBroad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
Luis M BrancoZalgen Labs, Frederick, MD, USA.
Lansana KannehViral Hemorrhagic Fever Program, Kenema Government Hospital, Ministry of Health and Sanitation, Kenema, Sierra Leone.
Joseph J VittiBroad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
Nisha BroodieNew York-Presbyterian Hospital-Columbia and Cornell, New York, NY, USA.
Adrianne Gladden-YoungMolecular Microbiology, Graduate School of Biomedical Sciences, Tufts University, Boston, MA, USA.
Omowunmi OmoniwaMalaria Consortium, Abuja, Nigeria.
Pan-Pan JiangGoogle Medical Brain, Mountain View, CA, USA.
Nathan YozwiakGene and Cell Therapy Institute, Mass General Brigham, Cambridge, MA, USA.
Shannon HeuklomSan Francisco Community Health Center, San Francisco, CA, USA.
Lina M MosesTulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA.
George O AkpedeInstitute of Lassa Fever, Research and Control, Irrua Specialist Teaching Hospital, Irrua, Nigeria.
Danny A AsogunDepartment of Community Medicine, Ambrose Alli University, Ekpoma, Nigeria.
Kathleen RubinsNational Aeronautics and Space Administration, Houston, TX, USA.
Susan KalesThe Jackson Laboratory, Bar Harbor, ME, USA.ORCID http://orcid.org/0000-0002-9903-7027
Anise N HappiAfrican Centre of Excellence for Genomics of Infectious Diseases (ACEGID), Redeemer's University, Ede, Nigeria.
Christopher O IruolagbeDepartment of Medicine, Irrua Specialist Teaching Hospital, Irrua, Nigeria.
Mercy Dic-IjiewereDepartment of Medicine, Irrua Specialist Teaching Hospital, Irrua, Nigeria.
Kelly IraoyahDepartment of Medicine, Irrua Specialist Teaching Hospital, Irrua, Nigeria.
Omoregie O OsazuwaDepartment of Medicine, Irrua Specialist Teaching Hospital, Irrua, Nigeria.
Alexander K OkonkwoDepartment of Medicine, Irrua Specialist Teaching Hospital, Irrua, Nigeria.
Stefan KunzInstitute of Microbiology, University Hospital Center and University of Lausanne, Lausanne, Switzerland.
Joseph B McCormickUTHealth Houston School of Public Health, Brownsville Campus, Brownsville, TX, USA.ORCID http://orcid.org/0000-0002-5844-8102
S Humarr KhanCollege of Medicine and Allied Health Sciences, University of Sierra Leone, Freetown, Sierra Leone.
Anna N HonkoBoston University School of Medicine, Boston, MA, USA.ORCID http://orcid.org/0000-0001-9165-148X
Eric S LanderBroad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
Michael B A OldstoneDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.ORCID http://orcid.org/0000-0003-0804-0501
Lisa HensleyNational Institutes of Health Integrated Research Facility, Frederick, MA, USA.
Onikepe A FolarinAfrican Centre of Excellence for Genomics of Infectious Diseases (ACEGID), Redeemer's University, Ede, Nigeria.ORCID http://orcid.org/0000-0001-7283-2920
Sylvanus A OkogbeninInstitute of Lassa Fever, Research and Control, Irrua Specialist Teaching Hospital, Irrua, Nigeria.
Stephan GüntherBernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.ORCID http://orcid.org/0000-0002-6562-0230
Hanna M OllilaBroad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
Ryan TewheyThe Jackson Laboratory, Bar Harbor, ME, USA.ORCID http://orcid.org/0000-0002-4607-8001
Peter O OkokhereInstitute of Lassa Fever, Research and Control, Irrua Specialist Teaching Hospital, Irrua, Nigeria.
John S SchieffelinSection of Infectious Disease, Department of Pediatrics, Tulane University School of Medicine, New Orleans, LA, USA.
Kristian G AndersenDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.ORCID http://orcid.org/0000-0001-6431-5982
Steven K ReillyDepartment of Genetics, Yale School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0003-3140-1483
Donald S GrantCollege of Medicine and Allied Health Sciences, University of Sierra Leone, Freetown, Sierra Leone.ORCID http://orcid.org/0000-0002-4329-0795
Robert F GarryTulane University School of Medicine, New Orleans, LA, USA.ORCID http://orcid.org/0000-0002-5683-3250
Kayla G BarnesBroad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-8291-4388
Christian T HappiAfrican Centre of Excellence for Genomics of Infectious Diseases (ACEGID), Redeemer's University, Ede, Nigeria. happic@run.edu.ng.ORCID http://orcid.org/0000-0002-3056-6705
Pardis C SabetiBroad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA. pardis@broadinstitute.org.ORCID http://orcid.org/0000-0002-9843-1890
Broad Institute · USIrrua Specialist Teaching Hospital · NGUniversity of Sierra Leone · SLRedeemer's University · NGScripps Research Institute · USTulane University · USJackson Laboratory · USAmbrose Alli University · NGBernhard Nocht Institute for Tropical Medicine · DECommunity Health Center · USGoogle (United States) · USHarvard University · USHoward Hughes Medical Institute · USJP Laboratories (United States) · USMass General Brigham · USNational Aeronautics and Space Administration · USNational Institutes of Health · USNewYork–Presbyterian Hospital · USThe University of Texas Health Science Center at Houston · USTufts University · US
Funding
Medical Scientist Training ProgramT32GM007753 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WALENSKY, LOREN DAVID · 1985 to 2021
$50.0MTechnology CoreU19AI135995 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI Kristian Graugaard Andersen · 2018 to 2026
$32.0MHigh-throughput systematic characterization of regulatory element functionUM1HG009436 · NHGRI · STANFORD UNIVERSITY · PI BASSIK, MICHAEL C, GREENLEAF, WILLIAM JAMES · 2017 to 2021
$5.4MElucidating Genetic Determinants of Resistance to Lassa Hemorrhagic FeverR01AI114855 · NIAID · BROAD INSTITUTE, INC. · PI SABETI, PARDIS CHRISTINE · 2015 to 2019
$3.8MFunctional Mapping of Enhancer Conservation Between Species to Enable Mechanistic Insights into Polygenic DiseaseR35HG011329 · NHGRI · JACKSON LABORATORY · PI TEWHEY, RYAN · 2021 to 2025
$2.6MHost and Pathogen Evolution in Lassa FeverDP2OD006514 · OD · HARVARD UNIVERSITY · PI SABETI, PARDIS CHRISTINE · 2010 to 2010
$2.5MHost and Microbial Genetic Determinants of Febrile Illness in West AfricaU01HG007480 · NHGRI · REDEEMER'S UNIVERSITY · PI HAPPI, CHRISTIAN T. · 2013 to 2016
$1.6MNHGRI NIH HHS R35 HG011329NHGRI NIH HHS U01 HG007480NHGRI NIH HHS UM1 HG009436NIAID NIH HHS R01 AI114855NIAID NIH HHS U19 AI135995NIGMS NIH HHS T32 GM007753NIH HHS DP2 OD006514
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.
Indexed as
Lassa FeverFeverGenome-Wide Association StudyHuman GeneticsHumansLassa virusSeroepidemiologic Studies
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