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.

中文翻译：

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EDAR、LYPLAL1、PRDM16、PAX3、DKK1、TNFSF12、CACNA2D3 和 SUPT3H 基因变异影响欧亚人群的面部形态。


在人类社会中，面部表面是基于面部形状变化而可见和可识别的，面部形状变化代表了一组高度多基因且相关的复杂特征。了解面部形状特征的遗传基础对于群体遗传学、发育生物学和法医学具有重要意义。许多单核苷酸多态性 (SNP) 与人类面部形状变异相关，尤其是在欧洲人群中。为了弥合欧洲和亚洲人群在面部形状变异的遗传基础方面的差距，我们研究了这些 SNP 在欧洲-亚洲混合欧亚人群（总共包括 612 个人）中的影响。 17 个面部标志的坐标源自高分辨率 3dMD 面部图像，并定量导出所有标志对之间的 136 个欧几里得距离。使用 Illumina Infinium Global Screening Array 对 DNA 样本进行基因分型，并使用 1000 Genomes 参考面板进行估算。使用线性回归测试了 125 个先前报道的面部形状相关 SNP 和 136 个面部形状表型之间的遗传关联。结果，在调整多重测试后，来自不同位点的总共 8 个 SNP 表现出与一种或多种面部形状特征显着相关（显着性阈值 p < 1.28 × 10-3），共同解释了高达 6.47% 的性别、年龄和体重指数调整的面部表型差异。其中包括 EDAR rs3827760、LYPLAL1 rs5781117、PRDM16 rs4648379、PAX3 rs7559271、DKK1 rs1194708、TNFSF12 rs80067372、CACNA2D3 rs56063440 和 SUPT3H rs227833。值得注意的是，EDAR rs3827760 和 LYPLAL1 rs5781117 SNP 分别与八种和七种面部表型显着相关 (2.39 × 10-5 < p < 1.28×10-3）。这些 SNP 中的大多数显示出千人基因组计划的欧洲和东亚参考组之间不同的等位基因频率。这些结果表明上述八个基因的细节影响欧亚人群的面部形状变化。