Key susceptibility locus for nonsyndromic cleft lip with or without cleft palate on chromosome 8q24

Stefanie Birnbaum, Kerstin U. Ludwig, Heiko Reutter, Stefan Herms, Michael Steffens, Michele Rubini, Carlotta Baluardo, Melissa Ferrian, Nilma Almeida de Assis, Margrieta A. Alblas, Sandra Barth, Jan Freudenberg, Carola Lauster, Guel Schmidt, Martin Scheer, Bert Braumann, Stefaan J. Berge, Rudolf H. Reich, Franziska Schiefke, Alexander HemprichSimone Poetzsch, Regine P. Steegers-Theunissen, Bernd Poetzsch, Susanne Moebus, Bernhard Horsthemke, Franz-Josef Kramer, Thomas F. Wienker, Peter A. Mossey, Peter Propping, Sven Cichon, Per Hoffmann, Michael Knapp, Markus M. Noethen, Elisabeth Mangold

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    Abstract

    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 x 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.

    Original languageEnglish
    Pages (from-to)473-477
    Number of pages5
    JournalNature Genetics
    Volume41
    Issue number4
    DOIs
    Publication statusPublished - Apr 2009

    Keywords

    • GENOME-WIDE ASSOCIATION
    • GENETIC-VARIANTS
    • EXPRESSION
    • RISK
    • IRF6
    • METAANALYSIS
    • DISEASE
    • DESIGN
    • CANCER
    • SCAN

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