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This study aimed to investigate the causal relationship between specific genetic loci related to m\n 6<\/jats:sup>\n A and dental caries.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Caries-associated genetic loci and signaling pathways were explored by integrating publicly available single-nucleotide polymorphism (SNP) association data, m\n 6<\/jats:sup>\n A quantitative trait locus (m\n 6<\/jats:sup>\n 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\n 6<\/jats:sup>\n A-related genetic variants and dental caries.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Among 29,797 m\n 6<\/jats:sup>\n A-SNPs analyzed, four reached genome-wide significance (\n P<\/jats:italic>\n \u2009<\u20095.0E-05), with rs3829225 showing the most significant association (\n P<\/jats:italic>\n \u2009=\u20091.23E-06). The rs2259956 variant demonstrated significant\n cis<\/jats:italic>\n -expression quantitative trait locus (cis-eQTL) effects on\n ABHD12<\/jats:italic>\n expression (\n z<\/jats:italic>\n score\u2009=\u200919.072,\n P<\/jats:italic>\n \u2009=\u20094.35E-81) and was predicted to enhance m\n 6<\/jats:sup>\n 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\n ABHD12<\/jats:italic>\n significantly upregulated in carious samples. Gene set enrichment analysis identified oxidative phosphorylation as the top enriched pathway (FDR\u2009<\u20090.05). Two-sample MR analysis (161,113 cases, 216,164 controls) revealed causal relationships between 15 immune cell traits and dental caries, with CD62L\n \u2212<\/jats:sup>\n dendritic cells increasing dental caries risk (OR\u2009=\u20091.019, 95% CI 1.004\u20131.035,\n P<\/jats:italic>\n \u2009=\u20091.6E-02) and plasmacytoid dendritic cells showing protective effects (OR\u2009=\u20090.978, 95% CI 0.965\u20130.991,\n P<\/jats:italic>\n \u2009=\u20091.0E-03).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n This study presents new evidence characterizing m\n 6<\/jats:sup>\n 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.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1186\/s40001-025-03514-2","type":"journal-article","created":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T10:35:28Z","timestamp":1766572528000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Characterization of m6A-regulated targets and immune cells in dental caries: insights from multi-omics analysis"],"prefix":"10.1186","volume":"30","author":[{"given":"Xi","family":"Zhou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyue","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yelin","family":"Mao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingling","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengfei","family":"Jiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,24]]},"reference":[{"issue":"4","key":"3514_CR1","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1177\/00220345211056247","volume":"101","author":"PYF Wen","year":"2022","unstructured":"Wen PYF, Chen MX, Zhong YJ, Dong QQ, Wong HM. 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