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.

doi.org/10.1038/ng.333, hdl.handle.net/1765/15338
Nature Genetics
Erasmus MC: University Medical Center Rotterdam

Birnbaum, S., Ludwig, K., Reutter, H., Herms, S., Steffens, M., Rubini, M., … Mangold, E. (2009). Key susceptibility locus for nonsyndromic cleft lip with or without cleft palate on chromosome 8q24. Nature Genetics, 41(4), 473–477. doi:10.1038/ng.333