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, Hensley, Lisa, Folarin, Onikepe A, Okogbenin, Sylvanus A, Günther, Stephan, Ollila, Hanna M, Tewhey, Ryan, Okokhere, Peter O, Schieffelin, John S, Andersen, Kristian G, Reilly, Steven K, Grant, Donald S, Garry, Robert F, Barnes, Kayla, Happi, Christian T and Sabeti, Pardis C (2024) 'Genome-wide association study identifies human genetic variants associated with fatal outcome from Lassa fever'. Nature Microbiology, Vol 9, pp. 751-762.

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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.

Item Type:	Article
Subjects:	QU Biochemistry > Genetics > QU 470 Genetic structures QU Biochemistry > Genetics > QU 475 Genetic processes QW Microbiology and Immunology > Viruses > QW 160 Viruses (General). Virology WC Communicable Diseases > Virus Diseases > Viral Hemorrhagic Fevers. Other Virus Diseases > WC 540 Neurotropic virus diseases
Faculty: Department:	Biological Sciences > Vector Biology Department
Digital Object Identifer (DOI):	https://doi.org/10.1038/s41564-023-01589-3
SWORD Depositor:	JISC Pubrouter
Depositing User:	JISC Pubrouter
Date Deposited:	22 Feb 2024 09:48
Last Modified:	12 Mar 2024 15:51
URI:	https://archive.lstmed.ac.uk/id/eprint/24071

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