Sallah, Neneh, Miley, Wendell, Labo, Nazzarena et al. (17 more authors) (2020) Distinct genetic architectures and environmental factors associate with host response to the γ2-herpesvirus infections. Nature Communications. 3849. ISSN 2041-1723
Abstract
Kaposi’s sarcoma-associated herpesvirus (KSHV) and Epstein-Barr Virus (EBV) establish life-long infections and are associated with malignancies. Striking geographic variation in incidence and the fact that virus alone is insufficient to cause disease, suggests other co-factors are involved. Here we present epidemiological analysis and genome-wide association study (GWAS) in 4365 individuals from an African population cohort, to assess the influence of host genetic and non-genetic factors on virus antibody responses. EBV/KSHV co-infection (OR = 5.71(1.58–7.12)), HIV positivity (OR = 2.22(1.32–3.73)) and living in a more rural area (OR = 1.38(1.01–1.89)) are strongly associated with immunogenicity. GWAS reveals associations with KSHV antibody response in the HLA-B/C region (p = 6.64 × 10−09). For EBV, associations are identified for VCA (rs71542439, p = 1.15 × 10−12). Human leucocyte antigen (HLA) and trans-ancestry fine-mapping substantiate that distinct variants in HLA-DQA1 (p = 5.24 × 10−44) are driving associations for EBNA-1 in Africa. This study highlights complex interactions between KSHV and EBV, in addition to distinct genetic architectures resulting in important differences in pathogenesis and transmission.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2020, The Author(s). |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Health Sciences (York) |
Depositing User: | Pure (York) |
Date Deposited: | 04 Aug 2020 12:00 |
Last Modified: | 16 Oct 2024 16:51 |
Published Version: | https://doi.org/10.1038/s41467-020-17696-2 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1038/s41467-020-17696-2 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:164003 |
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