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

ISSN
1061-4036
Date Issued
2009
Author(s)
Birnbaum, Stefanie
Ludwig, Kerstin U.
Reutter, Heiko
Herms, Stefan
Steffens, Michael
Rubini, Michele
Baluardo, Carlotta
Ferrian, Melissa
Assis, Nilma Almeida de
Alblas, Margrieta A.
Barth, Sandra
Freudenberg, Jan
Lauster, Carola
Schmidt, Guel
Scheer, Martin
Braumann, Bert
Bergé, Stefaan J.
Reich, Rudolf H.
Schiefke, Franziska
Hemprich, Alexander
Poetzsch, Simone
Steegers-Theunissen, Regine P.
Poetzsch, Bernd
Moebus, Susanne
Horsthemke, Bernhard
Wienker, Thomas F.
Mossey, Peter A.
Propping, Peter
Cichon, Sven
Hoffmann, Per
Knapp, Michael
Noethen, Markus M.
Mangold, Elisabeth
DOI
10.1038/ng.333
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.