EB 病毒 (EBV) 的基因变异与华南地区的鼻咽癌 (NPC) 密切相关。然而，不同的研究报告了关于最重要的病毒变异（EBER2 和 BALF2​​ 基因座多态性）的不同结果。在这项研究中，我们新测序了来自 61 个鼻咽癌病例和 39 个人群对照的 100 个 EBV 基因组。对华南地区鼻咽癌患者和健康携带者的 EBV 序列进行了全面的基因组分析，共计 279 例病例和 227 例对照。全基因组关联研究的荟萃分析显示，EBER2 下游的 4 bp 缺失（坐标，7188-7191；EBER-del）是与 NPC 相关的最显着的变异。此外，发现多种病毒变异体与形成风险单倍型的 EBER-del 存在遗传关联，这表明多种病毒变异体可能与 NPC 发病机制有关。群体结构和系统发育分析进一步表征了 NPC 的高风险 EBV 谱系，揭示了一组 38 个单核苷酸多态性 (SNP)，包括 EBER2 和 BALF2​​ 位点中的单核苷酸多态性 (SNP)。通过连锁不平衡聚类和特征选择算法，可以将38个SNP缩小到9个，可用于准确检测高风险EBV谱系。总之，我们的研究通过定义用于下游功能研究的 EBV 风险单倍型，并确定以 9 个 SNP 为特征的单一高风险 EBV 谱系，用于 NPC 人群筛查的潜在应用，为 EBV 遗传变异在 NPC 发病机制中的作用提供了新的见解。版权所有：© 2024 Wong 等人。这是一篇根据知识共享署名许可条款分发的开放获取文章，允许在任何媒体上不受限制地使用、分发和复制，前提是注明原始作者和来源。

Genetic variants in Epstein-Barr virus (EBV) have been strongly associated with nasopharyngeal carcinoma (NPC) in South China. However, different results regarding the most significant viral variants, with polymorphisms in EBER2 and BALF2 loci, have been reported in separate studies. In this study, we newly sequenced 100 EBV genomes derived from 61 NPC cases and 39 population controls. Comprehensive genomic analyses of EBV sequences from both NPC patients and healthy carriers in South China were conducted, totaling 279 cases and 227 controls. Meta-analysis of genome-wide association study revealed a 4-bp deletion downstream of EBER2 (coordinates, 7188-7191; EBER-del) as the most significant variant associated with NPC. Furthermore, multiple viral variants were found to be genetically linked to EBER-del forming a risk haplotype, suggesting that multiple viral variants might be associated with NPC pathogenesis. Population structure and phylogenetic analyses further characterized a high risk EBV lineage for NPC revealing a panel of 38 single nucleotide polymorphisms (SNPs), including those in the EBER2 and BALF2 loci. With linkage disequilibrium clumping and feature selection algorithm, the 38 SNPs could be narrowed down to 9 SNPs which can be used to accurately detect the high risk EBV lineage. In summary, our study provides novel insight into the role of EBV genetic variation in NPC pathogenesis by defining a risk haplotype of EBV for downstream functional studies and identifying a single high risk EBV lineage characterized by 9 SNPs for potential application in population screening of NPC.Copyright: © 2024 Wong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.