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In contrast to successes achieved for the other common form of orofacial clefting, that is, nonsyndromic cleft lip with\/without cleft palate (nsCL\/P), genome wide association studies (GWAS) of nsCPO have identified only one genome wide significant locus. Aim of the present study was to investigate whether common variants contribute to nsCPO and, if so, to identify novel risk loci.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We genotyped 33 SNPs at 27 candidate loci from 2 previously published nsCPO GWAS in an independent multiethnic sample. It included: (i) a family\u2010based sample of European ancestry (<jats:italic>n<\/jats:italic>\u2009=\u2009212); and (ii) two case\/control samples of Central European (<jats:italic>n<\/jats:italic>\u2009=\u200994\/339) and Arabian ancestry (<jats:italic>n<\/jats:italic>\u2009=\u200938\/231), respectively. A separate association analysis was performed for each genotyped dataset, and meta\u2010analyses were performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>After association analysis and meta\u2010analyses, none of the 33 SNPs showed genome\u2010wide significance. Two variants showed nominally significant association in the imputed GWAS dataset and exhibited a further decrease in <jats:italic>p<\/jats:italic>\u2010value in a European and an overall meta\u2010analysis including imputed GWAS data, respectively (rs395572: P<jats:sub>MetaEU<\/jats:sub>\u2009=\u20093.16 \u00d7 10<jats:sup>\u22124<\/jats:sup>; rs6809420: P<jats:sub>MetaAll<\/jats:sub>\u2009=\u20092.80 \u00d7 10<jats:sup>\u22124<\/jats:sup>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings suggest that there is a limited contribution of common variants to nsCPO. However, the individual effect sizes might be too small for detection of further associations in the present sample sizes. Rare variants may play a more substantial role in nsCPO than in nsCL\/P, for which GWAS of smaller sample sizes have identified genome\u2010wide significant loci. Whole\u2010exome\/genome sequencing studies of nsCPO are now warranted.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdr2.1213","type":"journal-article","created":{"date-parts":[[2018,3,2]],"date-time":"2018-03-02T05:52:51Z","timestamp":1519969971000},"page":"871-882","source":"Crossref","is-referenced-by-count":15,"title":["Nonsyndromic cleft palate: An association study at GWAS candidate loci in a multiethnic sample"],"prefix":"10.1002","volume":"110","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9836-554X","authenticated-orcid":false,"given":"Nina","family":"Ishorst","sequence":"first","affiliation":[{"name":"Department of Genomics, Life &amp; Brain Center University of Bonn Bonn Germany"},{"name":"Institute of Human Genetics University of Bonn Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Francheschelli","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Specialty Surgical Sciences, Section of Medical Biochemistry, Molecular Biology and Genetics University of Ferrara Ferrara Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5716-786X","authenticated-orcid":false,"given":"Anne C.","family":"B\u00f6hmer","sequence":"additional","affiliation":[{"name":"Department of Genomics, Life &amp; Brain Center University of Bonn Bonn Germany"},{"name":"Institute of Human Genetics University of Bonn Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Faisal J.","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Specialty Surgical Sciences, Section of Medical Biochemistry, Molecular Biology and Genetics University of Ferrara Ferrara Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Heilmann\u2010Heimbach","sequence":"additional","affiliation":[{"name":"Department of Genomics, Life &amp; Brain Center University of Bonn Bonn Germany"},{"name":"Institute of Human Genetics University of Bonn Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine","family":"Fricker","sequence":"additional","affiliation":[{"name":"Department of Genomics, Life &amp; Brain Center University of Bonn Bonn Germany"},{"name":"Institute of Human Genetics University of Bonn Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian","family":"Little","sequence":"additional","affiliation":[{"name":"School of Epidemiology, Public Health and Preventive Medicine University of Ottawa Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regine P.M.","family":"Steegers\u2010Theunissen","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Department of Pediatrics, Division Neonatology Erasmus MC University Medical Center Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Borut","family":"Peterlin","sequence":"additional","affiliation":[{"name":"Department of Obstetrics &amp; Gynecology, Clinical Institute of Medical Genetics University Medical Center Ljubljana Ljubljana Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Nowak","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University of Bonn Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Martini","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillo\u2010Facial\u2010Plastic Surgery University of Bonn Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Kruse","sequence":"additional","affiliation":[{"name":"Department of Orthodontics University of Cologne Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anton","family":"Dunsche","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillo\u2010Facial Surgery Clinics Karlsruhe Karlsruhe Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Kreusch","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Head and Neck Centre Asklepios Klinik Nord\u2010Heidberg Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"G\u00f6lz","sequence":"additional","affiliation":[{"name":"Department of Orthodontics University of Bonn Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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\/0000-0002-1894-470X","authenticated-orcid":false,"given":"Esam","family":"Halboub","sequence":"additional","affiliation":[{"name":"Department of Maxillofacial Surgery and Diagnostic Sciences, Devision of Oral Medicine and Diagnostic Sciences College of Dentistry, Jazan University Jazan Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3591-5265","authenticated-orcid":false,"given":"Heiko","family":"Reutter","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University of Bonn Bonn Germany"},{"name":"Department of Neonatology, Children's Hospital University of Bonn Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Mossey","sequence":"additional","affiliation":[{"name":"Dental Hospital University of Dundee Dundee United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus M.","family":"N\u00f6then","sequence":"additional","affiliation":[{"name":"Department of Genomics, Life &amp; 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