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

• Published in: Global health, epidemiology and genomics Vol. 2; p. e18
• Main Authors: Sallah, N., Carstensen, T., Wakeham, K., Bagni, R., Labo, N., Pollard, M. O., Gurdasani, D., Ekoru, K., Pomilla, C., Young, E. H., Fatumo, S., Asiki, G., Kamali, A., Sandhu, M., Kellam, P., Whitby, D., Barroso, I., Newton, R.
• Format: Journal Article
• Language: English
• Published: Cambridge, UK Cambridge University Press 2017
• Subjects: Antibody response; Antigens; Antiviral agents; Association analysis; Biomedical research; Cancer; DQA1 protein; Epstein-Barr virus; Ethics; Gene mapping; Genetic diversity; Genetics; Genome-wide association studies; Genomes; Genomics; Genotyping; Histocompatibility antigen HLA; Immunoglobulin G; Immunoglobulins; Infections; Laboratories; Lymphoma; Medical research; Nucleotide sequence; Original; Original Research Article; Population; Population studies; Principal components analysis; Quality control; Studies; Viral infections; United Kingdom > UK; United States > US; Uganda; genomics; Epstein-Barr virus; immunity; infectious disease; Africa
• ISSN: 2054-4200; 2054-4200
• DOI: 10.1017/gheg.2017.16

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.