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Whole-genome association study of antibody response to Epstein-Barr virus in an African population: a pilot

  • N. Sallah (a1) (a2), T. Carstensen (a1) (a3), K. Wakeham (a4) (a5), R. Bagni (a6), N. Labo (a7), M. O. Pollard (a1) (a3), D. Gurdasani (a1) (a3), K. Ekoru (a1) (a3), C. Pomilla (a1) (a3), E. H. Young (a1) (a3), S. Fatumo (a1) (a3) (a8), G. Asiki (a4), A. Kamali (a4), M. Sandhu (a1) (a3), P. Kellam (a2), D. Whitby (a7), I. Barroso (a1) and R. Newton (a4)...
Abstract
Abstract

Epstein Barr virus (EBV) infects 95% of the global population and is associated with up to 2% of cancers globally. Immunoglobulin G (IgG) antibody levels to EBV have been shown to be heritable and associated with developing malignancies. We, therefore, performed a pilot genome-wide association analysis of anti-EBV IgG traits in an African population, using a combined approach including array genotyping, whole-genome sequencing and imputation to a panel with African sequence data. In 1562 Ugandans, we identify a variant in human leukocyte antigen (HLA)-DQA1, rs9272371 (p = 2.6 × 10−17) associated with anti-EBV nuclear antigen-1 responses. Trans-ancestry meta-analysis and fine-mapping with European-ancestry individuals suggest the presence of distinct HLA class II variants driving associations in Uganda. In addition, we identify four putative, novel, very rare African-specific loci with preliminary evidence for association with anti-viral capsid antigen IgG responses which will require replication for validation. These findings reinforce the need for the expansion of such studies in African populations with relevant datasets to capture genetic diversity.

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Copyright
This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited
Corresponding author
*Address for correspondence: Inês Barroso, Department of Human Genetics, Wellcome Trust Sanger Institute, Hinxton CB10 1HH, UK. (Email: ib1@sanger.ac.uk)
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These authors contributed equally to this work.

Footnotes
References
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