Appraising the life‐course impact of Epstein‐Barr virus exposure and its genetic signature on periodontitis

作者：Xinjian Ye, Jian Yuan, Yijing Bai, Yitong Chen, He Jiang, Yue Cao, Qi Ge, Zhiyong Wang, Weiyi Pan, Shan Wang, Qianming Chen · 发表于：Journal of Periodontology · 年份：2024 · DOI：10.1002/jper.24-0300 · 被引用次数：7 · 研究领域：Oral microbiology and periodontitis research、Genetic Associations and Epidemiology、Viral-associated cancers and disorders

Abstract Background Periodontitis arises from a multifaceted interplay of environmental variables and genetic susceptibility, where microbial infection plays an indispensable part. Epstein‐Barr virus (EBV) exposure has long been considered associated with periodontitis activity; however, the causal relationship and genetic connection between them remain unknown. Methods Within a life‐course context, our study employed comprehensive Mendelian randomization (MR) methods, including univariable, multivariable, Bayesian model averaging, and reverse MR, to investigate the causal association between EBV exposure and periodontitis. Additionally, linkage disequilibrium score regression and colocalization analysis were utilized to assess the cross‐trait genetic correlations, followed by transcriptome‐wide association and enrichment analysis to discern the genetic‐phenotypic biological profiles. Results Heightened levels of EBV antibodies, particularly early antigen diffuses (which serve as indicators of early infection or reactivation), are associated with an increased risk of periodontitis (odds ratio [OR]: 1.27 [1.09–1.47], p = 6.05 × 10 −3 ) and demonstrate a significant genetic correlation ( p = 4.11 × 10 −3 ). This pathogenesis may involve the high‐confidence causal gene RNASEK located in 17p13.1. Genetically predicted early‐life anti‐EBV immunoglobulin G (IgG) levels are correlated to a reduced periodontitis risk (OR: 0.89 [0.82–0.97], p = 1.76 × 10 −3 ). Conclusions The present ...