SNPs at three loci (HMGA2, ADK and AJUBA) showed evidence of association with craniofacial distances, particularly those indexing facial width. The SNP rs17101923 is located in an intron of the gene HMGA2 which is known to contain genetic variants associated with height (29), head circumference (36), intracranial volume (37) and permanent dentition (7). The top variant from our study (rs17101923) is in moderate to high LD with these genetic variants, which could reflect the pleiotropic action on growth, in general, of a single causal variant. Ligon et al. (38) report the case of an 8-year-old boy with a de novo pericentric inversion of chromosome 12 that truncated the HMGA2 gene. The patient exhibited multiple clinical features, including premature dentition, enlarged and supernumerary teeth, as well as macrocephaly, flat supraorbital ridges, widely spaced eyes and prominent alveolar ridges. Our results suggest that common SNPs at this locus can also contribute to normal variation in the timing of tooth eruption and craniofacial distances.
