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Background <p>Dental caries is one of the most common oral diseases worldwide. <i>N</i><sup>6</sup>-Methyladenosine (m<sup>6</sup>A), a type of RNA modification, plays an important role in various biological processes and cellular responses. This study aimed to investigate the causal relationship between specific genetic loci related to m<sup>6</sup>A and dental caries.</p> Methods <p>Caries-associated genetic loci and signaling pathways were explored by integrating publicly available single-nucleotide polymorphism (SNP) association data, m<sup>6</sup>A quantitative trait locus (m<sup>6</sup>A-QTL) data from genome-wide association studies (GWAS), and single-cell RNA sequencing data derived from the dental pulp of healthy individuals and patients with dental caries. Mendelian randomization (MR) was also used to explore the causal relationship between m<sup>6</sup>A-related genetic variants and dental caries.</p> Results <p>Among 29,797 m<sup>6</sup>A-SNPs analyzed, four reached genome-wide significance (<i>P</i> &lt; 5.0E-05), with rs3829225 showing the most significant association (<i>P</i> = 1.23E-06). The rs2259956 variant demonstrated significant <i>cis</i>-expression quantitative trait locus (cis-eQTL) effects on <i>ABHD12</i> expression (<i>z</i> score = 19.072, <i>P</i> = 4.35E-81) and was predicted to enhance m<sup>6</sup>A modification (score change: 0.588 to 0.595). Single-cell RNA sequencing of 53,595 cells revealed that dendritic cells mainly existed in the carious pulp and showed the highest fold-change, with <i>ABHD12</i> significantly upregulated in carious samples. Gene set enrichment analysis identified oxidative phosphorylation as the top enriched pathway (FDR &lt; 0.05). Two-sample MR analysis (161,113 cases, 216,164 controls) revealed causal relationships between 15 immune cell traits and dental caries, with CD62L<sup>−</sup>dendritic cells increasing dental caries risk (OR = 1.019, 95% CI 1.004–1.035, <i>P</i> = 1.6E-02) and plasmacytoid dendritic cells showing protective effects (OR = 0.978, 95% CI 0.965–0.991, <i>P</i> = 1.0E-03).</p> Conclusions <p>This study presents new evidence characterizing m<sup>6</sup>A-related SNPs in increasing dental caries susceptibility and provides a single-cell transcriptomic profiling of dental caries with insights into the relationship between dental caries and immune cells.</p>

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Characterization of m6A-regulated targets and immune cells in dental caries: insights from multi-omics analysis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月24日

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  • Xi Zhou,
  • Cheng Shi,
  • Kang Li,
  • Siyue Yao,
  • Lan Ma,
  • Yelin Mao,
  • Lingling Jiang,
  • Pengfei Jiao

摘要

Background

Dental caries is one of the most common oral diseases worldwide. N6-Methyladenosine (m6A), a type of RNA modification, plays an important role in various biological processes and cellular responses. This study aimed to investigate the causal relationship between specific genetic loci related to m6A and dental caries.

Methods

Caries-associated genetic loci and signaling pathways were explored by integrating publicly available single-nucleotide polymorphism (SNP) association data, m6A quantitative trait locus (m6A-QTL) data from genome-wide association studies (GWAS), and single-cell RNA sequencing data derived from the dental pulp of healthy individuals and patients with dental caries. Mendelian randomization (MR) was also used to explore the causal relationship between m6A-related genetic variants and dental caries.

Results

Among 29,797 m6A-SNPs analyzed, four reached genome-wide significance (P < 5.0E-05), with rs3829225 showing the most significant association (P = 1.23E-06). The rs2259956 variant demonstrated significant cis-expression quantitative trait locus (cis-eQTL) effects on ABHD12 expression (z score = 19.072, P = 4.35E-81) and was predicted to enhance m6A modification (score change: 0.588 to 0.595). Single-cell RNA sequencing of 53,595 cells revealed that dendritic cells mainly existed in the carious pulp and showed the highest fold-change, with ABHD12 significantly upregulated in carious samples. Gene set enrichment analysis identified oxidative phosphorylation as the top enriched pathway (FDR < 0.05). Two-sample MR analysis (161,113 cases, 216,164 controls) revealed causal relationships between 15 immune cell traits and dental caries, with CD62L−dendritic cells increasing dental caries risk (OR = 1.019, 95% CI 1.004–1.035, P = 1.6E-02) and plasmacytoid dendritic cells showing protective effects (OR = 0.978, 95% CI 0.965–0.991, P = 1.0E-03).

Conclusions

This study presents new evidence characterizing m6A-related SNPs in increasing dental caries susceptibility and provides a single-cell transcriptomic profiling of dental caries with insights into the relationship between dental caries and immune cells.