A genome-wide association study of facial morphology identifies novel genetic loci in Han Chinese

Yin Huang,Dan Li,Lu Qiao,Yu Liu,Qianqian Peng,Sijie Wu,Manfei Zhang,Yajun Yang,Jingze Tan,Shuhua Xu,Li Jin,Sijia Wang,Kun Tang,Stefan Grünewald

doi:10.1016/j.jgg.2020.10.004

Abstract

The human face is a heritable surface with many complex sensory organs. In recent years, many genetic loci associated with facial features have been reported in different populations, yet there is a lack of studies on the Han Chinese population. Here, we report a genome-wide association study of 3D normal human faces of 2,659 Han Chinese with autosegment phenotypes of facial morphology. We identify single-nucleotide polymorphisms (SNPs) encompassing four genomic regions showing significant associations with different facial regions, including SNPs in DENND1B associated with the chin, SNPs among PISRT1 associated with eyes, SNPs between DCHS2 and SFRP2 associated with the nose, and SNPs in VPS13B associated with the nose. We replicate 24 SNPs from previously reported genetic loci in different populations, whose candidate genes are DCHS2, SUPT3H, HOXD1, SOX9, PAX3, and EDAR. These results provide a more comprehensive understanding of the genetic basis of variation in human facial morphology.

Highlights

The human face encompasses complex sensory organs and shows remarkable variation in facial traits
We found genetic variants associated with nose and eyes through a large-scale high-resolution 3D facial genetic study on the Han Chinese population
We noted that genes (DCHS2 and SFRP2) related to one of these loci are differentially expressed in human and chimp cranial neural crest cells, which plays a crucial role in the early formation of facial morphology

Summary

Introduction

The human face encompasses complex sensory organs and shows remarkable variation in facial traits. A GWAS in Latin Americans reported five more genetic variants close to DCHS2, RUNX2, GLI3, PAX1, and EDAR related to nose shape (Adhikari et al, 2016) Another recent GWAS (Shaffer et al, 2016) identified seven additional genetic variants for face traits such as facial width and depth, and nose shape in European-derived cohort. There were some GWAS studies carried out on normal human facial morphology in different populations, including Europeans (Liu et al, 2012; Paternoster et al, 2012; Shaffer et al, 2016; Lee et al, 2017; Claes et al, 2018; Crouch et al, 2018), Latin Americans (Adhikari et al, 2016), Africans (Cole et al, 2016) and Asians (Cha et al, 2018; Qiao et al, 2018). We observed that different regions of the nose received precise regulation of genetic variants

Methods

Results

Discussion

Conclusion