{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T01:39:16Z","timestamp":1783820356961,"version":"3.55.0"},"reference-count":40,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2019,12,7]],"date-time":"2019-12-07T00:00:00Z","timestamp":1575676800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000782","name":"European Science Foundation","doi-asserted-by":"publisher","award":["09-RNP-023"],"award-info":[{"award-number":["09-RNP-023"]}],"id":[{"id":"10.13039\/501100000782","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015902","name":"European Orthodontic Society","doi-asserted-by":"publisher","award":["1"],"award-info":[{"award-number":["1"]}],"id":[{"id":"10.13039\/100015902","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["LU1944-3\/1"],"award-info":[{"award-number":["LU1944-3\/1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Non-syndromic cleft lip with or without cleft palate (nsCL\/P) ranks among the most common human congenital malformations, and has a multifactorial background in which both exogenous and genetic risk factors act in concert. The present report describes a genome-wide association study (GWAS) involving a total of 285 nsCL\/P patients and 1212 controls from the Netherlands and Belgium. Twenty of the 40 previously reported nsC\/LP susceptibility loci were replicated, which underlined the validity of this sample. SNV-based analysis of the data identified an as yet unreported suggestive locus at chromosome 16p12.1 (p-value of the lead SNV: 4.17 \u00d7 10\u22127). This association was replicated in two of three patient\/control replication series (Central European and Yemeni). Gene analysis of the GWAS data prioritized SH3PXD2A at chromosome 10q24.33 as a candidate gene for nsCL\/P. To date, support for this gene as a cleft gene has been restricted to data from zebrafish and a knockout mouse model. The present GWAS was the first to implicate SH3PXD2A in non-syndromic cleft formation in humans. In summary, although performed in a relatively small sample, the present GWAS generated novel insights into nsCL\/P etiology.<\/jats:p>","DOI":"10.3390\/genes10121023","type":"journal-article","created":{"date-parts":[[2019,12,9]],"date-time":"2019-12-09T05:54:51Z","timestamp":1575870891000},"page":"1023","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Non-Syndromic Cleft Lip with or without Cleft Palate: Genome-Wide Association Study in Europeans Identifies a Suggestive Risk Locus at 16p12.1 and Supports SH3PXD2A as a Clefting Susceptibility Gene"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9519-966X","authenticated-orcid":false,"given":"Iris ALM","family":"van Rooij","sequence":"first","affiliation":[{"name":"Department for Health Evidence, Radboud Institute for Health Sciences, Radboud university medical center, 6500 HB Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8541-2519","authenticated-orcid":false,"given":"Kerstin U","family":"Ludwig","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University of Bonn, 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Welzenbach","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University of Bonn, 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Ishorst","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University of Bonn, 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Thonissen","sequence":"additional","affiliation":[{"name":"Department of Dentistry, Radboud Institute for Health Sciences, Section of Orthodontics and Craniofacial Biology, Radboud university medical center, 6500 HB Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tessel E","family":"Galesloot","sequence":"additional","affiliation":[{"name":"Department for Health Evidence, Radboud Institute for Health Sciences, Radboud university medical center, 6500 HB Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edwin","family":"Ongkosuwito","sequence":"additional","affiliation":[{"name":"Department of Dentistry, Radboud Institute for Health Sciences, Section of Orthodontics and Craniofacial Biology, Radboud university medical center, 6500 HB Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefaan J","family":"Berg\u00e9","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Radboud university medical center, 6500 HB Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5920-8004","authenticated-orcid":false,"given":"Khalid","family":"Aldhorae","sequence":"additional","affiliation":[{"name":"Orthodontic Department, College of Dentistry, Thamar University, Thamar, Yemen"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3765-6778","authenticated-orcid":false,"given":"Augusto","family":"Rojas-Martinez","sequence":"additional","affiliation":[{"name":"Tecnologico de Monterrey, School of Medicine, and Universidad Autonoma de Nuevo Leon, Centro de Investigaci\u00f3n y Desarrollo en Ciencias de la Salud, Monterrey 64460, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lambertus ALM","family":"Kiemeney","sequence":"additional","affiliation":[{"name":"Department for Health Evidence, Radboud Institute for Health Sciences, Radboud university medical center, 6500 HB Nijmegen, The Netherlands"},{"name":"Department of Urology, Radboud Institute for Health Sciences, Radboud university medical center, 6500 HB Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joris Robert","family":"Vermeesch","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Brunner","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, and Donders Institute for Brain, Cognition and Behaviour, Radboud university medical center, 6500 HB Nijmgen, The Netherlands"},{"name":"Department of Clinical Genetics, and GROW School for Oncology and Developmental Biology, Maastricht University Medical Center, 6202 AZ Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nel","family":"Roeleveld","sequence":"additional","affiliation":[{"name":"Department for Health Evidence, Radboud Institute for Health Sciences, Radboud university medical center, 6500 HB Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koen","family":"Devriendt","sequence":"additional","affiliation":[{"name":"Center for Human Genetics, University Hospitals Leuven, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Titiaan","family":"Dormaar","sequence":"additional","affiliation":[{"name":"Department of Imaging and Pathology, KU Leuven, 3000 Leuven, Belgium"},{"name":"Oral and Maxillofacial Surgery, University Hospitals Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greet","family":"Hens","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Experimental Otorhinolaryngology, KU Leuven, 3000 Leuven, 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