{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T13:01:07Z","timestamp":1777813267836,"version":"3.51.4"},"reference-count":36,"publisher":"SAGE Publications","issue":"12","license":[{"start":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T00:00:00Z","timestamp":1747008000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T00:00:00Z","timestamp":1747008000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100013373","name":"nihr oxford biomedical research centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013373","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP23K09149"],"award-info":[{"award-number":["JP23K09149"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Dent Res"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:p>\n                    Orofacial cleft (OFC) is a common congenital anomaly in humans with variable birth prevalence in different ethnic groups. Although genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) associated with nonsyndromic OFC (nsOFC), understanding of the underlying biological mechanisms of causative SNPs and genes in nsOFC remains limited. Here, we report that the noncoding SNP, rs3741442, has an expression quantitative trait locus (eQTL) effect on epithelial genes associated with periderm differentiation. Using a combination of epigenetic markers and\n                    <jats:italic toggle=\"yes\">in silico<\/jats:italic>\n                    analysis, we prioritized the intergenic SNP rs3741442 as a potential causal factor in nsOFC. The risk allele of rs3741442 is prevalent in East Asian populations, and its presence in CRISPR-edited cells leads to reduced expression of neighboring\n                    <jats:italic toggle=\"yes\">KRT18<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">EIF4B.<\/jats:italic>\n                    The transcription factor SP1 differentially binds the risk versus nonrisk alleles of rs3741442. Alongside this\n                    <jats:italic toggle=\"yes\">cis<\/jats:italic>\n                    -eQTL impact, rs3741442 has a\n                    <jats:italic toggle=\"yes\">trans<\/jats:italic>\n                    -eQTL effect on the epithelial gene\n                    <jats:italic toggle=\"yes\">TP63<\/jats:italic>\n                    that is associated with syndromic forms of OFC and psoriasis. These findings provide insights into the mechanism by which an intergenic SNP can affect palatogenesis through the modulation of gene expression.\n                  <\/jats:p>","DOI":"10.1177\/00220345251334385","type":"journal-article","created":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T02:23:28Z","timestamp":1747189408000},"page":"1385-1394","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["The Functional Impact of the Noncoding SNP rs3741442 on Orofacial Clefting"],"prefix":"10.1177","volume":"104","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1320-3304","authenticated-orcid":false,"given":"N.","family":"Funato","sequence":"first","affiliation":[{"name":"Department of Signal Gene Regulation, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Tokyo, Japan"},{"name":"Research Infrastructure Management Center, Institute of Science Tokyo, Tokyo, Japan"},{"name":"Oral Science Center, Institute of Science Tokyo, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5024-049X","authenticated-orcid":false,"given":"S.R.F.","family":"Twigg","sequence":"additional","affiliation":[{"name":"Clinical Genetics Group, MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK"},{"name":"NIHR Oxford Biomedical Research Centre, Oxford, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2025,5,12]]},"reference":[{"key":"e_1_3_3_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.d2090"},{"key":"e_1_3_3_3_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.215160.116"},{"key":"e_1_3_3_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddy402"},{"key":"e_1_3_3_5_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.03265"},{"key":"e_1_3_3_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.723885"},{"issue":"24","key":"e_1_3_3_7_1","first-page":"4218","article-title":"Overexpression of Grainyhead-like 3 causes spina bifida and interacts genetically with mutant alleles of Grhl2 and Vangl2 in mice","volume":"27","author":"De Castro SCP","year":"2018","unstructured":"De Castro SCP, Gustavsson P, Marshall AR, Gordon WM, Galea G, Nikolopoulou E, Savery D, Rolo A, Stanier P, Andersen B, et al. 2018. Overexpression of Grainyhead-like 3 causes spina bifida and interacts genetically with mutant alleles of Grhl2 and Vangl2 in mice. 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Ever-changing landscapes: transcriptional enhancers in development and evolution. Cell. 167(5):1170\u20131187.","DOI":"10.1016\/j.cell.2016.09.018"},{"key":"e_1_3_3_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.archoralbio.2022.105372"},{"key":"e_1_3_3_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.13.5670"},{"issue":"4","key":"e_1_3_3_20_1","first-page":"513","article-title":"The role of the ubiquitously expressed transcription factor Sp1 in tissue-specific transcriptional regulation and in disease","volume":"89","author":"O\u2019Connor L","year":"2016","unstructured":"O\u2019Connor L, Gilmour J, Bonifer C. 2016. The role of the ubiquitously expressed transcription factor Sp1 in tissue-specific transcriptional regulation and in disease. 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