State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China.
Department of Plastic Surgery, The First Hospital of Jilin University, Changchun, 130000, People's Republic of China.
BMC Med. 2023 Dec 5;21(1):487. doi: 10.1186/s12916-023-03142-9.
Glioma is one of the leading types of brain tumor, but few etiologic factors of primary glioma have been identified. Previous observational research has shown an association between viral infection and glioma risk. In this study, we used Mendelian randomization (MR) analysis to explore the direction and magnitude of the causal relationship between viral infection and glioma.
We conducted a two-sample bidirectional MR analysis using genome-wide association study (GWAS) data. Summary statistics data of glioma were collected from the largest meta-analysis GWAS, involving 12,488 cases and 18,169 controls. Single-nucleotide polymorphisms (SNPs) associated with exposures were used as instrumental variables to estimate the causal relationship between glioma and twelve types of viral infections from corresponding GWAS data. In addition, sensitivity analyses were performed.
After correcting for multiple tests and sensitivity analysis, we detected that genetically predicted herpes zoster (caused by Varicella zoster virus (VZV) infection) significantly decreased risk of low-grade glioma (LGG) development (OR = 0.85, 95% CI: 0.76-0.96, P = 0.01, FDR = 0.04). No causal effects of the other eleven viral infections on glioma and reverse causality were detected.
This is one of the first and largest studies in this field. We show robust evidence supporting that genetically predicted herpes zoster caused by VZV infection reduces risk of LGG. The findings of our research advance understanding of the etiology of glioma.
脑肿瘤是最主要的脑肿瘤类型之一，但目前仅识别出少数原发性脑肿瘤的病因因素。既往观察性研究表明病毒感染与脑肿瘤风险之间存在关联。在这项研究中，我们使用孟德尔随机化（MR）分析来探讨病毒感染与脑肿瘤之间的因果关系的方向和程度。
我们使用全基因组关联研究（GWAS）数据进行两样本双向 MR 分析。脑肿瘤的汇总统计数据来自最大的荟萃分析 GWAS，涉及 12488 例病例和 18169 例对照。将与暴露相关的单核苷酸多态性（SNP）用作工具变量，以从相应的 GWAS 数据中估计脑肿瘤与 12 种病毒感染之间的因果关系。此外，还进行了敏感性分析。
经过多重检验校正和敏感性分析，我们发现遗传预测的带状疱疹（由水痘带状疱疹病毒（VZV）感染引起）显著降低了低级别胶质瘤（LGG）的发病风险（OR=0.85，95%CI：0.76-0.96，P=0.01，FDR=0.04）。未检测到其他 11 种病毒感染对脑肿瘤的因果作用和反向因果关系。
这是该领域首次也是规模最大的研究之一。我们提供了强有力的证据支持 VZV 感染引起的遗传预测带状疱疹可降低 LGG 的发病风险。我们的研究结果增进了对脑肿瘤病因的理解。
