In a previous genome-wide meta-analysis of primary tooth eruption, we identified five loci associated with ‘age at first tooth’ and ‘number of teeth’ at 1 year of age at genome-wide levels of significance, and a further five at suggestive levels of significance (6). Many of these loci contained genes previously implicated in tooth or other organ development. A more recent GWAS of secondary tooth eruption identified two of the same loci as well as two others containing the genes ADK and CACNA1S/TMEM9 (7). What was particularly striking about both studies was the number of loci displaying large effect sizes. Typically, GWASs of quantitative traits require tens of thousands of individuals to identify common variants of small effect. However, the tooth eruption phenotype appears to be influenced by some loci of comparably large effect (i.e. >1% of the phenotypic variance), implying that the genome-wide study of primary tooth eruption might be a powerful strategy not only at detecting variants involved in dentition, but also SNPs that may exert pleiotropic actions on other aspects of growth and development.
