(Figure 2—figure supplements 1–6 show six novel replicated loci, Figure 2—figure supplements 7–17 show 11 novel non-replicated loci, Figure 2—figure supplements 18–24 show seven previously reported loci) (A) From up to down, the 1st panel shows regional association plots (LocusZoom) for the top-associated facial phenotypes with candidate genes aligned below according to the chromosomal positions (GRCh37.p13). The 2nd panel shows signals of local positive selection using diversity (FST) and conservation (|iHS|) statistics between and within EUR, AFR, and EAS population samples from the 1000 Genomes Project. The 3rd panel denotes the linkage disequilibrium (LD) patterns (r2) in the associated region. The 4th panel shows epigenetic annotation of CNCC’s regulatory elements in corresponding regions using WashU Epigenome Browser. Chip-seq profiles display histone modifications associated with active enhancers (H3K27ac, H3K4me1) or promoters (H3K4me3), and binding of general coactivator p300 and transcription factor TFAP2A. The ATAC-seq track shows chromatin accessibility. The PhyloP track indicates cross-species conservation. (B) Shows a face map denoting the significance (-log10P) for the associations between the top SNP and facial phenotypes. The dashed line means that the P value was nominally significant (p<0.01) but did not reach study-wide suggestive significance (p>5e-8). (C) Effect sizes for the derived allele at index SNPs. Blue, red, and green boxes represent effect sizes estimated in the participating discovery cohort, combined meta-analysis, and in the replication UYG cohort, respectively. Box sizes are proportional to sample size. Horizontal bars indicate a 95% confidence interval of width equal to 1.96 standard errors. (D) All SNPs in LD (r2 > 0.25) with the top-associated SNP and all base-pairs in vicinity (within 20 kb, p<0.05) are displayed according to their log scaled quantile rank (-log10p, axis scale) in the circular figure below, where the rank is calculated using the Chip-seq values in the whole genome. In addition, SNPs associated with facial phenotypes in our meta-analysis of GWASs were highlighted according to their association p values (PMeta, color scale) and their LD (r2) with the top-associated SNP in the region (points size). Association, selection, LD and regulation patterns for rs143353512 located around CASZ1.