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Despite the identification of many genetic loci harboring OFC-risk variants, there are many unknown genetic determinants of OFC. Furthermore, while the process of embryonic facial development is well characterized, the molecular mechanisms that underly it are not. This represents a major hurdle in understanding how disruptions in these biological processes result in OFC. Thus, we sought to identify novel OFC-risk loci through a genome-wide multi-ancestry study of five nested OFC phenotypes (isolated cleft lip [CLO], isolated cleft palate [CPO], cleft lip and palate [CLP], cleft lip with\/without cleft palate [CL\/P], and any cleft [ANY]) representing distinct cleft subtypes to identify subtype-specific signals and grouped types to maximize power to detect shared genetic effects. We performed genome-wide meta-analyses of these five OFC phenotypes from three cohorts totaling &gt;14,000 individuals using METAL. In addition to replicating 13 known OFC-risk loci, we observed novel association in three regions: the 1p36.32 locus (lead variant rs584402, an intergenic variant, p\n                    <jats:sub>CLO<\/jats:sub>\n                    \u2009=\u20093.14e-8), the 7q33 locus (lead variant rs17168118, an intronic variant in\n                    <jats:italic>CALD1<\/jats:italic>\n                    , p\n                    <jats:sub>CLP<\/jats:sub>\n                    \u2009=\u20099.17e-9), and the 16p13.3 locus (lead variant rs77075754, an intronic variant in\n                    <jats:italic>RBFOX1<\/jats:italic>\n                    , p\n                    <jats:sub>CL\/P\u2009<\/jats:sub>\n                    =\u20091.53e-9, p\n                    <jats:sub>ANY<\/jats:sub>\n                    \u2009=\u20091.93e-9). We also observed a novel association within the known risk locus 8q22.1 that was independent of the previously reported signal (lead variant rs4735314, an intronic variant in\n                    <jats:italic>ESRP1<\/jats:italic>\n                    , p\n                    <jats:sub>CLP<\/jats:sub>\n                    \u2009=\u20091.07e-9, p\n                    <jats:sub>CL\/P<\/jats:sub>\n                    \u2009=\u20093.88e-8). Next, we performed multi-tissue TWAS with s-MulTiXcan and identified four overlapping genes with significant genetically predicted transcription associated with OFC risk. These genes also overlapped the genome-wide significant association signals from the meta-analysis, including\n                    <jats:italic>CALD1<\/jats:italic>\n                    and\n                    <jats:italic>ESRP1<\/jats:italic>\n                    and known OFC-risk genes\n                    <jats:italic>TANC2<\/jats:italic>\n                    and\n                    <jats:italic>NTN1<\/jats:italic>\n                    . Each of the newly reported loci has potential regulatory effects, including evidence of craniofacial enhancer activity, that offer new clues as to the molecule mechanisms underlying embryonic facial development.\n                  <\/jats:p>","DOI":"10.1371\/journal.pgen.1011581","type":"journal-article","created":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T17:43:34Z","timestamp":1759254214000},"page":"e1011581","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["Variants in CALD1, ESRP1, and RBFOX1 are associated with orofacial cleft risk"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5483-0833","authenticated-orcid":true,"given":"Jenna 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Howe","year":"2019","journal-title":"Epigenomics"},{"issue":"6","key":"pgen.1011581.ref052","doi-asserted-by":"crossref","DOI":"10.1242\/dmm.050261","article-title":"Early embryogenesis in CHDFIDD mouse model reveals facial clefts and altered cranial neurogenesis","volume":"17","author":"M Hampl","year":"2024","journal-title":"Dis Model Mech"},{"issue":"1","key":"pgen.1011581.ref053","doi-asserted-by":"crossref","first-page":"4679","DOI":"10.1038\/s41467-019-12435-8","article-title":"Disruptive mutations in TANC2 define a neurodevelopmental syndrome associated with psychiatric disorders","volume":"10","author":"H Guo","year":"2019","journal-title":"Nat Commun"},{"issue":"12","key":"pgen.1011581.ref054","doi-asserted-by":"crossref","first-page":"104094","DOI":"10.1016\/j.ejmg.2020.104094","article-title":"17q23.3 de novo microdeletion involving only TANC2 gene: A new case","volume":"63","author":"E Tassano","year":"2020","journal-title":"Eur J Med Genet"},{"issue":"1","key":"pgen.1011581.ref055","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1186\/s12881-017-0479-3","article-title":"17q23.2q23.3 de novo duplication in association with speech and language disorder, learning difficulties, incoordination, motor skill impairment, and behavioral disturbances: a case report","volume":"18","author":"K Wessel","year":"2017","journal-title":"BMC Med Genet"},{"issue":"2","key":"pgen.1011581.ref056","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1016\/j.bbrc.2019.04.151","article-title":"Purification and mutagenesis studies of TANC1 ankyrin repeats domain provide clues to understand mis-sense variants from diseases","volume":"514","author":"Q Yang","year":"2019","journal-title":"Biochem Biophys Res Commun"},{"issue":"3","key":"pgen.1011581.ref057","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1002\/aur.2880","article-title":"Knockout of tanc2 causes autism-like behavior and sleep disturbance in 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studies","volume":"34","author":"CC Laurie","year":"2010","journal-title":"Genet Epidemiol"},{"issue":"7845","key":"pgen.1011581.ref061","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1038\/s41586-021-03205-y","article-title":"Sequencing of 53,831 diverse genomes from the NHLBI TOPMed Program","volume":"590","author":"D Taliun","year":"2021","journal-title":"Nature"},{"issue":"1","key":"pgen.1011581.ref062","doi-asserted-by":"crossref","DOI":"10.1186\/s13742-015-0047-8","article-title":"Second-generation PLINK: rising to the challenge of larger and richer datasets","volume":"4","author":"CC Chang","year":"2015","journal-title":"GigaScience"},{"issue":"24","key":"pgen.1011581.ref063","doi-asserted-by":"crossref","first-page":"5346","DOI":"10.1093\/bioinformatics\/btz567","article-title":"Genetic association testing using the GENESIS R\/Bioconductor package","volume":"35","author":"SM Gogarten","year":"2019","journal-title":"Bioinformatics"},{"key":"pgen.1011581.ref064","unstructured":"Conomos MP, Gogarten SM, Brown L, Chen H, Rice K, Sofer T. GENESIS: GENetic EStimation and Inference in Structured samples (GENESIS): Statistical methods for analyzing genetic data from samples with population structure and\/or relatedness. 2019. https:\/\/github.com\/UW-GAC\/GENESIS"},{"issue":"1","key":"pgen.1011581.ref065","doi-asserted-by":"crossref","first-page":"1826","DOI":"10.1038\/s41467-017-01261-5","article-title":"Functional mapping and annotation of genetic associations with FUMA","volume":"8","author":"K Watanabe","year":"2017","journal-title":"Nat Commun"},{"issue":"1","key":"pgen.1011581.ref066","doi-asserted-by":"crossref","first-page":"1825","DOI":"10.1038\/s41467-018-03621-1","article-title":"Exploring the phenotypic consequences of tissue specific gene expression variation inferred from GWAS summary statistics","volume":"9","author":"AN Barbeira","year":"2018","journal-title":"Nature Communications"},{"issue":"8","key":"pgen.1011581.ref067","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1002\/gepi.22346","article-title":"Fine-mapping and QTL tissue-sharing information improves the reliability of causal gene identification","volume":"44","author":"AN Barbeira","year":"2020","journal-title":"Genet Epidemiol"},{"issue":"1","key":"pgen.1011581.ref068","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1007889","article-title":"Integrating predicted transcriptome from multiple tissues improves association detection","volume":"15","author":"AN Barbeira","year":"2019","journal-title":"PLoS Genet"}],"updated-by":[{"DOI":"10.1371\/journal.pgen.1011581","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T00:00:00Z","timestamp":1759795200000}}],"container-title":["PLOS Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pgen.1011581","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T18:01:37Z","timestamp":1759860097000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pgen.1011581"}},"subtitle":[],"editor":[{"given":"Yun","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,9,30]]},"references-count":68,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,9,30]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pgen.1011581","relation":{},"ISSN":["1553-7404"],"issn-type":[{"value":"1553-7404","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,30]]}}}