We conducted a genome-wide association study involving 224 patients and 383 controls of Central European origin in order to identify novel susceptibility loci for non-syndromic cleft lip with or without cleft palate (NSCL/P). A 640-kb region at chromosome 8q24.21 was found to contain multiple markers with strongly significant evidence for association with the cleft phenotype, including four markers which 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 patients 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.
Key susceptibility locus for nonsyndromic cleft lip with or without cleft palate on chromosome 8q24
RUBINI, Michele;BALUARDO, Carlotta;FERRIAN, Melissa;
2009
Abstract
We conducted a genome-wide association study involving 224 patients and 383 controls of Central European origin in order to identify novel susceptibility loci for non-syndromic cleft lip with or without cleft palate (NSCL/P). A 640-kb region at chromosome 8q24.21 was found to contain multiple markers with strongly significant evidence for association with the cleft phenotype, including four markers which 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 patients 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.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
