A highly significant sex effect (min p=2.1 × 10 −151 ) and aging effect (min p=8.0 × 10 −44 ) were noted, together explained up to 21% of the variance per facial phenotype (e.g. between alares and Ls; Figure 1—figure supplement 2A–2C , Supplementary file 1 - Table 3).
In general, no significant heterogeneity was observed for the 24 top SNPs of the study-wide significant and suggestive associated loci, that is only one SNP (rs3403289 at 2q36.1 PAX3 ) showed nominally significant (Cochran's Q test p=0.04, Table 1 ) heterogeneity between the discovery cohorts, but was not significant after multiple testing correction.