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

作者：Birnbaum Stefanie; Ludwig Kerstin U; Reutter Heiko; Herms Stefan; Steffens Michael; Rubini Michele; Baluardo Carlotta; Ferrian Melissa; de Assis Nilma Almeida; Alblas Margrieta A; Barth Sandra; Freudenberg Jan; Lauster Carola; Schmidt Guel; Scheer Martin; Braumann Bert; Berge Stefaan J; Reich Rudolf H; Schiefke Franziska; Hemprich Alexander; Poetzsch Simone; Steegers Theunissen Regine P; Poetzsch Bernd; Moebus Susanne; Horsthemke Bernhard; Kramer Franz Josef

来源：Nature Genetics, 2009, 41(4): 473-477.

DOI：10.1038/ng.333

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.

• 出版日期2009-4
• 单位河北医科大学