Family‐based study shows heterogeneity of a susceptibility locus on chromosome 8q24 for nonsyndromic cleft lip and palate

Abstract

Nonsyndromic cleft lip with or without cleft palate is a common birth defect. Although a number of susceptibility loci have been reported, replication has often been lacking. This is likely due, in part, to the heterogeneity of datasets and methodologies. Two independent genome-wide association studies of individuals of largely western European extraction have identified a possible susceptibility locus on 8q24.21. To determine the overall effect of this locus, we genotyped six of the previously associated single nucleotide polymorphisms in our Hispanic and non-Hispanic white family-based datasets and evaluated them for linkage and association. In addition, we genotyped a large African American family with nonsyndromic cleft lip with or without cleft palate that we had previously mapped to the 8q21.3-24.12 region to test for linkage. There was no evidence for linkage to this region in any of the three ethnic groups. Nevertheless, strong evidence for association was noted in the non-Hispanic white group, whereas none was detected in the Hispanic dataset. These results confirm the previously reported association and provide evidence suggesting that there is ethnically based heterogeneity for this locus.