EDAR, LYPLAL1, PRDM16, PAX3, DKK1, TNFSF12, CACNA2D3, and SUPT3H gene variants influence facial morphology in a Eurasian population

Abstract

In human society, the facial surface is visible and recognizable based on the facial shape variation which represents a set of highly polygenic and correlated complex traits. Understanding the genetic basis underlying facial shape traits has important implications in population genetics, developmental biology, and forensic science. A number of single nucleotide polymorphisms (SNPs) are associated with human facial shape variation, mostly in European populations. To bridge the gap between European and Asian populations in term of the genetic basis of facial shape variation, we examined the effect of these SNPs in a European-Asian admixed Eurasian population which included a total of 612 individuals. The coordinates of 17 facial landmarks were derived from high resolution 3dMD facial images, and 136 Euclidean distances between all pairs of landmarks were quantitatively derived. DNA samples were genotyped using the Illumina Infinium Global Screening Array and imputed using the 1000 Genomes reference panel. Genetic association between 125 previously reported facial shape-associated SNPs and 136 facial shape phenotypes was tested using linear regression. As a result, a total of eight SNPs from different loci demonstrated significant association with one or more facial shape traits after adjusting for multiple testing (significance threshold p < 1.28 × 10^-3), together explaining up to 6.47% of sex-, age-, and BMI-adjusted facial phenotype variance. These included EDAR rs3827760, LYPLAL1 rs5781117, PRDM16 rs4648379, PAX3 rs7559271, DKK1 rs1194708, TNFSF12 rs80067372, CACNA2D3 rs56063440, and SUPT3H rs227833. Notably, the EDAR rs3827760 and LYPLAL1 rs5781117 SNPs displayed significant association with eight and seven facial phenotypes, respectively (2.39 × 10^-5 < p < 1.28 × 10^-3). The majority of these SNPs showed a distinct allele frequency between European and East Asian reference panels from the 1000 Genomes Project. These results showed the details of above eight genes influence facial shape variation in a Eurasian population.