Letter abstract
Nature Genetics 41, 473 - 477 (2009)
Published online: 8 March 2009 | doi:10.1038/ng.333
Key susceptibility locus for nonsyndromic cleft lip with or without cleft palate on chromosome 8q24
Stefanie Birnbaum1,2,19, Kerstin U Ludwig3,19, Heiko Reutter1, Stefan Herms3, Michael Steffens4, Michele Rubini5, Carlotta Baluardo5, Melissa Ferrian5, Nilma Almeida de Assis1, Margrieta A Alblas3, Sandra Barth3, Jan Freudenberg6, Carola Lauster7, Gül Schmidt7, Martin Scheer8, Bert Braumann9, Stefaan J Bergé10, Rudolf H Reich11, Franziska Schiefke12, Alexander Hemprich12, Simone Pötzsch13, Regine P Steegers-Theunissen14, Bernd Pötzsch15, Susanne Moebus16, Bernhard Horsthemke17, Franz-Josef Kramer2, Thomas F Wienker4, Peter A Mossey18, Peter Propping1, Sven Cichon1,3, Per Hoffmann1,3, Michael Knapp4, Markus M Nöthen1,3,19 & Elisabeth Mangold1,19
We conducted a genome-wide association study involving 224 cases and 383 controls of Central European origin to identify susceptibility loci for nonsyndromic cleft lip with or without cleft palate (NSCL/P). A 640-kb region at chromosome 8q24.21 was found to contain multiple markers with highly significant evidence for association with the cleft phenotype, including three markers that reached genome-wide significance. The 640-kb cleft-associated region was saturated with 146 SNP markers and then analyzed in our entire NSCL/P sample of 462 unrelated cases and 954 controls. In the entire sample, the most significant SNP (rs987525) had a P value of 3.34 
10-24. The odds ratio was 2.57 (95% CI = 2.02–3.26) for the heterozygous genotype and 6.05 (95% CI = 3.88–9.43) for the homozygous genotype. The calculated population attributable risk for this marker is 0.41, suggesting that this study has identified a major susceptibility locus for NSCL/P.
- Institute of Human Genetics, University of Bonn, Bonn, Germany.
- Department of Oral and Maxillofacial Surgery, University of Göttingen, Göttingen, Germany.
- Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany.
- Institute of Medical Biometry, Informatics and Epidemiology, University of Bonn, Bonn, Germany.
- Department of Experimental and Diagnostic Medicine, Medical Genetics Unit, University of Ferrara, Ferrara, Italy.
- Center for Genomics & Human Genetics, Feinstein Institute for Medical Research, Northshore-LIJ University Hospital, New York, USA.
- Department of Cleft Lip and Cleft Palate Surgery, Humboldt University of Berlin, Berlin, Germany.
- Department of Oral and Maxillo-Facial Surgery, University of Cologne, Cologne, Germany.
- Department of Orthodontics, University of Cologne, Cologne, Germany.
- Department of Oral and Maxillo-Facial Surgery, Radboud University Nijmegen, Nijmegen, The Netherlands.
- Department of Oral and Maxillo-Facial-Plastic Surgery, University of Bonn, Bonn, Germany.
- Department of Oral and Maxillo-Facial Surgery, University of Leipzig, Leipzig, Germany.
- Monitoring of Congenital Malformations Saxony Anhalt, University of Magdeburg, Magdeburg, Germany.
- University Medical Center, Rotterdam, The Netherlands.
- Institute of Experimental Hematology and Transfusion Medicine, University of Bonn, Bonn, Germany.
- Institute for Medical Informatics, Biometry and Epidemiology, University Hospital of Essen, University Duisburg-Essen, Germany.
- Institute of Human Genetics, University Hospital of Essen, University Duisburg-Essen, Germany.
- Orthodontic Unit, Dental Hospital & School, University of Dundee, Dundee, UK.
- These authors contributed equally to this work.
Correspondence to: Elisabeth Mangold1,19 e-mail: e.mangold@uni-bonn.de
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