{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T10:19:06Z","timestamp":1755598746863,"version":"3.41.2"},"reference-count":35,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2024,10,15]],"date-time":"2024-10-15T00:00:00Z","timestamp":1728950400000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82301014","82270496","82101054"],"award-info":[{"award-number":["82301014","82270496","82101054"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20220309"],"award-info":[{"award-number":["BK20220309"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>N6\u2010methyladenosine (m<jats:sup>6<\/jats:sup>A) is the most prevalent modification of RNA in eukaryotes which is associated with many cellular processes and diseases. Here, our objective is to explore whether genetic variants in m<jats:sup>6<\/jats:sup>A modification genes are associated with the risk of non\u2010syndrome orofacial clefts (NSOCs).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The transmission disequilibrium test (TDT) was performed to calculate the association between single nucleotide polymorphisms (SNPs) in m<jats:sup>6<\/jats:sup>A modification genes and NSOCs risk in 944 case\u2010parent trios. The function of SNP was predicted by HaploReg, RegulomeDB and histone enrichment data. The expression quantitative trait locus (eQTL) analysis was examined using Genotype\u2010Tissue Expression (GTEx) and eQTLGen. The role of gene in the development of NSOCs was assessed with correlation and enrichment analysis based on gene expression data in mice craniofacial tissue and zebrafish embryo.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified that rs8078195 (A\u2009&gt;\u2009C) in <jats:italic>METTL16<\/jats:italic> was suggestively associated with the increased risk of NSOCs (OR\u2009=\u20091.32, <jats:italic>p<\/jats:italic>\u2009=\u20091.80E \u2212 03). The region surrounding rs8078195 was subjected to deoxyribonuclease hypersensitivity and enriched with multiple histone modifications. In addition, it had a significant eQTL effect with <jats:italic>METTL16<\/jats:italic> in skin tissue and human peripheral blood, which played an important role in NSOCs development. Bioinformatic analysis indicated that <jats:italic>METTL16<\/jats:italic> contributed to the development of NSOCs probably by regulating cell cycle process.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Rs8078195 in <jats:italic>METTL16<\/jats:italic> was associated with the occurrence of NSOCs.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdr2.2403","type":"journal-article","created":{"date-parts":[[2024,10,15]],"date-time":"2024-10-15T13:29:28Z","timestamp":1728998968000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Genetic Variants in <i>METTL16<\/i> Affect the Risk of Non\u2010Syndromic Orofacial Clefts"],"prefix":"10.1002","volume":"116","author":[{"given":"Xinze","family":"Xu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Cultivation Base of Research, Prevention and Treatment for Oral Diseases Nanjing Medical University  Nanjing China"},{"name":"Jiangsu Province Engineering Research Center of Stomatological Translational Medicine Nanjing Medical University  Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaofeng","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cultivation Base of Research, Prevention and Treatment for Oral Diseases Nanjing Medical University  Nanjing China"},{"name":"Jiangsu Province Engineering Research Center of Stomatological Translational Medicine Nanjing Medical University  Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minxuan","family":"Han","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cultivation Base of Research, Prevention and Treatment for Oral Diseases Nanjing Medical University  Nanjing China"},{"name":"Jiangsu Province Engineering Research Center of Stomatological Translational Medicine Nanjing Medical University  Nanjing China"},{"name":"Department of Orthodontics The Affiliated Stomatological Hospital of Nanjing Medical University  Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Changyue","family":"Xing","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cultivation Base of Research, Prevention and Treatment for Oral Diseases Nanjing Medical University  Nanjing China"},{"name":"Jiangsu Province Engineering Research Center of Stomatological Translational Medicine Nanjing Medical University  Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guirong","family":"Zhu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cultivation Base of Research, Prevention and Treatment for Oral Diseases Nanjing Medical University  Nanjing China"},{"name":"Jiangsu Province Engineering Research Center of Stomatological Translational Medicine Nanjing Medical University  Nanjing 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Medical University  Nanjing China"},{"name":"Department of Orthodontics The Affiliated Stomatological Hospital of Nanjing Medical University  Nanjing 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