Evidence map›Paper›PMID 41239515›Full record

ArticleClinical epigenetics2025

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

Lianjie Peng, Shengzhe Nie, Yihua Sun, Shihan Wang, Yaying Wang, Zhichao Liu

Abstract read
In one paragraph

Article in Clinical epigenetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

6 authors.

Lianjie Peng *Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Kaixuan Road 268, Hangzhou, 310020, Zhejiang Province, China.
Shengzhe Nie *Qilu Medical University, Zibo City, Shandong Province, China.
Yihua Sun *School of Stomatology, Nanchang University, Nanchang, Jiangxi Province, China.
Shihan WangStomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Kaixuan Road 268, Hangzhou, 310020, Zhejiang Province, China.
Yaying WangChangsha Medical University, Changsha, Hunan Province, China.
Zhichao LiuStomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Kaixuan Road 268, Hangzhou, 310020, Zhejiang Province, China. zhichaoliu@zju.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveThe 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.

methodsA 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.

resultsMR 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 = 1.128, 95% CI 1.036-1.230, p = 0.006). Reverse MR analysis identified a bidirectional causal relationship between oral lichen ruber planus and IEAA (OR = 1.127, 95% CI 1.006-1.263, p = 0.039). No significant associations were observed between epigenetic age acceleration and dental caries, recurrent aphthous ulcers, or oral leukoplakia (all p > 0.05). Sensitivity analyses confirmed the robustness of these findings. TWAS and SMR identified eight genes associated with the effect of GrimAge on periodontitis, six genes associated with the effect of PhenoAge on stomatitis, four genes associated with the effect of IEAA on oral lichen ruber planus and seven genes associated with the effect of lichen ruber planus on IEAA.

conclusionsThis study revealed causal relationships between epigenetic age acceleration and common oral diseases, and explored the relevant mechanisms, highlighting the potential novel strategies for prevention.

Indexed as

AgingEpigenesis, GeneticMendelian Randomization AnalysisMouth DiseasesAgedDNA MethylationEpigenomicsFemaleGenome-Wide Association StudyHumansMaleMiddle AgedPhenotypeQuantitative Trait LociEpigenetic age accelerationMendelian randomizationOral diseasesOral lichen ruber planusPeriodontitisStomatitis

Identifiers

PMID41239515
PMCPMC12619391

What Socratic holds

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.