Old Medical School, Usher Institute, University of Edinburgh, Teviot Place, Edinburgh, EH8 9AG, UK.
MRC Human Genetics Unit, Institute of Genetics and Cancer, Western General Hospital, University of Edinburgh, Crewe Road, Edinburgh, EH4 2XU, UK.
BMC Infect Dis. 2023 Feb 3;23(1):65. doi: 10.1186/s12879-023-08031-3.
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.
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.
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.
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.
Epstein Barr 病毒（EBV）在全球范围内感染了约 95%的人口，已知会导致不良健康后果，如霍奇金淋巴瘤、非霍奇金淋巴瘤和多发性硬化症。人们对开发预防 EBV 感染的疫苗有着浓厚的兴趣和投资。为了有效地部署这种疫苗，了解感染的危险因素至关重要。为什么某些人没有被感染目前尚不清楚。目前的文献描述了复杂的、常常相互交织的因素网络——社会人口统计学、临床、遗传、环境——使得因果关系难以解读。我们旨在使用孟德尔随机化（MR）来克服混杂和反向因果关系带来的问题，以确定 EBV 感染的因果风险因素。
在这项研究之前，我们将文献中描述的与 EBV 血清阳性状态（作为感染的替代指标）相关的复杂证据映射到因果关系图中，以确定我们研究的潜在风险因素。利用英国生物库中 8422 名年龄在 40 至 69 岁之间、被认为是白种英国人种的个体的基因组数据，这些个体在 2006 年至 2010 年期间被招募，我们对 EBV 血清阳性状态进行了全基因组关联研究（GWAS），随后进行了两样本 MR 分析，以确定哪些潜在风险因素是因果关系。
我们的 GWAS 确定了两个与 EBV 血清阳性状态相关的新基因座。在 MR 分析中，我们证实了受教育时间较短、性伴侣数量增加以及吸烟开始年龄较低是 EBV 血清阳性状态的因果风险因素。
鉴于当前对 EBV 疫苗的兴趣和未来可能出现的情况，这些因素可以通过完成因果关系的拼图，为疫苗的开发和部署策略提供信息。了解这些风险因素可以确定最有可能感染 EBV 的人群，深入了解何时接种疫苗以及引入疫苗时应优先考虑哪些人群。
