Unraveling the causal association of epigenetic age acceleration with common oral diseases and its underlying mechanisms: findings from Mendelian randomization and integrative genetic analysis

作者：Lianjie Peng, Shuai Nie, Yihua Sun, Shihan Wang, Yaying Wang, Zhichao Liu · 发表于：Clinical Epigenetics · 年份：2025 · DOI：10.1186/s13148-025-02005-9 · 被引用次数：3 · 研究领域：Genetic Associations and Epidemiology、Epigenetics and DNA Methylation、Oral and gingival health research

OBJECTIVE: The epigenetic clock is recognized as a highly accurate predictor of biological aging, but the relationship between epigenetic age acceleration and oral diseases remains poorly understood. This study aimed to investigate the causal associations between epigenetic age acceleration and oral diseases and identify the shared gene expressions. METHODS: A two-phase study design was used: in phase 1, we conducted MR analysis to investigate the association between epigenetic age acceleration and common oral diseases. In phase 2, we conducted transcriptome-wide association studies (TWAS) to identify gene expressions linked to phenotypes with positive outcomes. Subsequently, we performed summary-based MR (SMR) analyses integrating expression quantitative trait loci (eQTL) datasets to ascertain whether these gene expressions could affect the phenotypes. Finally, we performed biological pathway enrichment analysis to investigate the potential mechanisms. RESULTS: MR analysis revealed significant causal relationships between epigenetic age acceleration and oral diseases. Specifically, GrimAge was associated with an increased risk of periodontitis (OR = 1.160, 95% CI 1.010-1.333, p = 0.036 in FinnGen cohort; OR = 1.120, 95% CI 1.000-1.255, p = 0.049 in GLIDE consortium). PhenoAge showed a significant association with stomatitis (OR = 1.062, 95% CI 1.007-1.120, p = 0.026). Intrinsic epigenetic age acceleration (IEAA) was linked to a higher risk of oral lichen ruber planus (OR = 1...