We next investigated whether the SNPs at our top loci have pleiotropic effects, specifically whether they are associated with both primary tooth and craniofacial development. A recent GWAS investigated the genetic determinants of 54 measures of craniofacial shape and size recorded in ALSPAC (Supplementary Material, Fig. S4) (11). We used these data to test for association between the top SNPs at genome-wide significance and each of the 54 measures of craniofacial development. Because of the large number of correlated craniofacial phenotypes analysed, and consequently the large number of statistical tests performed, we calculated empirical P-values for each SNP permuting each genotype against the 54 phenotypes. This procedure is less conservative than a Bonferroni correction (which assumes that the phenotypes are independent) and ensures that the correlation between phenotypes is properly accounted for in the multiple testing correction. Empirical P-values were calculated for each SNP and those with P < 0.05 were declared significant (Table 2). Using this procedure, we identified three SNPs, which were associated with 10 of the 54 craniofacial measures. Specifically, the SNP rs17101923 (HMGA2) was associated with
