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Distinct genetic architectures and environmental factors associate with host response to the γ2-herpesvirus infections

Author

Listed:
  • Neneh Sallah

    (The Wellcome Sanger Institute, Wellcome Genome Campus
    London School of Hygiene & Tropical Medicine
    London School of Hygiene & Tropical Medicine)

  • Wendell Miley

    (Leidos Biomedical Research Inc.)

  • Nazzarena Labo

    (Leidos Biomedical Research Inc.)

  • Tommy Carstensen

    (The Wellcome Sanger Institute, Wellcome Genome Campus
    University of Cambridge)

  • Segun Fatumo

    (The Wellcome Sanger Institute, Wellcome Genome Campus
    London School of Hygiene & Tropical Medicine
    MRC/UVRI at the London School of Hygiene & Tropical Medicine)

  • Deepti Gurdasani

    (The Wellcome Sanger Institute, Wellcome Genome Campus
    Queen Mary University London)

  • Martin O. Pollard

    (The Wellcome Sanger Institute, Wellcome Genome Campus
    University of Cambridge)

  • Alexander T. Dilthey

    (Heinrich Heine University Düsseldorf)

  • Alexander J. Mentzer

    (University of Oxford
    University of Oxford)

  • Vickie Marshall

    (Leidos Biomedical Research Inc.)

  • Elena M. Cornejo Castro

    (Leidos Biomedical Research Inc.)

  • Cristina Pomilla

    (The Wellcome Sanger Institute, Wellcome Genome Campus
    University of Cambridge)

  • Elizabeth H. Young

    (The Wellcome Sanger Institute, Wellcome Genome Campus
    University of Cambridge)

  • Gershim Asiki

    (African Population and Health Research Center)

  • Martin L. Hibberd

    (London School of Hygiene & Tropical Medicine)

  • Manjinder Sandhu

    (University of Cambridge)

  • Paul Kellam

    (Imperial College London
    Kymab Ltd, Babraham Research Complex)

  • Robert Newton

    (MRC/UVRI at the London School of Hygiene & Tropical Medicine)

  • Denise Whitby

    (Leidos Biomedical Research Inc.)

  • Inês Barroso

    (The Wellcome Sanger Institute, Wellcome Genome Campus
    University of Cambridge
    University of Exeter Medical School)

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.

Suggested Citation

  • Neneh Sallah & Wendell Miley & Nazzarena Labo & Tommy Carstensen & Segun Fatumo & Deepti Gurdasani & Martin O. Pollard & Alexander T. Dilthey & Alexander J. Mentzer & Vickie Marshall & Elena M. Cornej, 2020. "Distinct genetic architectures and environmental factors associate with host response to the γ2-herpesvirus infections," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17696-2
    DOI: 10.1038/s41467-020-17696-2
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