Abstract
Background: Epstein Barr virus (EBV) infects ~ 95% of the population worldwide and is known to cause adverse health outcomes such as Hodgkin’s, non-Hodgkin’s lymphomas, and multiple sclerosis. There is substantial interest and investment in developing infection-preventing vaccines for EBV. To effectively deploy such vaccines, it is vital that we understand the risk factors for infection. Why particular individuals do not become infected is currently unknown. The current literature, describes complex, often conflicting webs of intersecting factors—sociodemographic, clinical, genetic, environmental-, rendering causality difficult to decipher. We aimed to use Mendelian randomization (MR) to overcome the issues posed by confounding and reverse causality to determine the causal risk factors for the acquisition of EBV.
Methods: We mapped the complex evidence from the literature prior to this study factors associated with EBV serostatus (as a proxy for infection) into a causal diagram to determine putative risk factors for our study. Using data from the UK Biobank of 8422 individuals genomically deemed to be of white British ancestry between the ages of 40 and 69 at recruitment between the years 2006 and 2010, we performed a genome wide association study (GWAS) of EBV serostatus, followed by a Two Sample MR to determine which putative risk factors were causal.
Results: Our GWAS identified two novel loci associated with EBV serostatus. In MR analyses, we confirmed shorter time in education, an increase in number of sexual partners, and a lower age of smoking commencement, to be causal risk factors for EBV serostatus.
Conclusions: Given the current interest and likelihood of a future EBV vaccine, these factors can inform vaccine development and deployment strategies by completing the puzzle of causality. Knowing these risk factors allows identification of those most likely to acquire EBV, giving insight into what age to vaccinate and who to prioritise when a vaccine is introduced.
| Original language | English |
|---|---|
| Article number | 65 |
| Number of pages | 9 |
| Journal | BMC Infectious Diseases |
| Volume | 23 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 3 Feb 2023 |
Bibliographical note
Funding Information:MDM’s Ph.D. is funded by the University of Edinburgh, UK. JFW acknowledges support from the MRC Human Genetics Unit programme grant, “Quantitative traits in health and disease” (U. MC_UU_00007/10). GT would like to acknowledge funding from Cancer Research UK award C8781/A13174. HRS is supported by the UK Medical Research Council (MRC) [MR/R008345/1]. NP has no funding to declare. Funding bodies had no responsibility for study design, data collection, analysis, interpretation of data or in writing of this manuscript.
This analysis of secondary data was sponsored by the Academic and Clinical Central Office for Research and Development (ACCORD) of the University of Edinburgh and National Health Service Lothian, UK (AC19175). The research conducted within this study was assessed using an Usher Institute, University of Edinburgh Level 1 Ethics Self-Audit, which demonstrated that it posed no reasonably foreseeable ethical risks and so was exempt from formal ethic review by the Usher Research Ethics Group. The UK Biobank genotypic and phenotypic data used in this study were approved under application 19655.
Publisher Copyright:
© 2023, The Author(s).
Keywords
- Epidemiology
- Epstein–Barr virus
- Mendelian randomization
- Public health
- Vaccination
ASJC Scopus subject areas
- Infectious Diseases
