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

Journal

Nature microbiology

ISSN: 2058-5276

Titre abrégé: Nat Microbiol

Pays: England

ID NLM: 101674869

Informations de publication

Date de publication:
07 Feb 2024

Historique:

received: 30 09 2022

accepted: 14 12 2023

medline: 8 2 2024

pubmed: 8 2 2024

entrez: 7 2 2024

Statut: aheadofprint

Résumé

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.

Identifiants

DOI: 10.1038/s41564-023-01589-3 PMID: 38326571

pubmed: 38326571

doi: 10.1038/s41564-023-01589-3

pii: 10.1038/s41564-023-01589-3

doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

Subventions

Organisme : NIAID NIH HHS

ID : HHSN272201000022C

Pays : United States

Informations de copyright

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