Genome-wide association study identifies human genetic variants associated with fatal outcome from Lassa fever
| dc.contributor.author | Folarin, Onikepe | |
| dc.date.accessioned | 2025-05-29T09:21:56Z | |
| dc.date.available | 2025-05-29T09:21:56Z | |
| dc.date.issued | 2024-02-07 | |
| dc.description.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. | |
| dc.description.sponsorship | National Institutes of Health grants R01AI114855 (P.C.S.), 1DP2OD006514 (P.C.S.), HHSN272201000022C (P.C.S.), U01HG007480 (C.T.H.), German Research Foundation grants GU 883/1-1 (S.G.), GU 883/4-1 (S.G.) and GU 883/4-2 (S.G.), and the Howard Hughes Medical Institute (P.C.S.). D.K. was supported by award number T32GM007753 from the National Institute of General Medical Sciences. S.R. was supported by the FujiFilm Fellowship from Harvard Medical School. | |
| dc.identifier.uri | 10.1038/s41564-023-01589-3 | |
| dc.identifier.uri | https://repository.run.edu.ng/handle/123456789/4988 | |
| dc.language.iso | en | |
| dc.publisher | Nature microbiology | |
| dc.relation.ispartofseries | 9 | |
| dc.title | Genome-wide association study identifies human genetic variants associated with fatal outcome from Lassa fever | |
| dc.type | Article |