Association Between Viral Infections and Glioma Risk: A Two-Sample Bidirectional Mendelian Randomization Analysis

Authors

Sheng Zhong
Wenzhuo Yang
Zhiyun Zhang
Yangyiran Xie
Lin Pan
Jiaxin Ren
Fei Ren
Yifan Li
Haoqun Xie
Hongyu Chen
Davy Deng
Jie Lu
Hui Li
Bo Wu
Youqi Chen
Fei Peng
Vinay K Puduvalli
Ke Sai
Yunqian Li
Ye Cheng
Yonggao Mou

Publication Date

12-5-2023

Journal

BMC Medicine

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords

Humans, Genome-Wide Association Study, Glioma, Herpes Zoster, Mendelian Randomization Analysis, Virus Diseases, Mendelian randomization, Viral infection, Risk, Glioma

DOI

10.1186/s12916-023-03142-9

PMID

38053181

PMCID

PMC10698979

PubMedCentral® Posted Date

12-5-2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes