Novel genetic loci affecting facial shape variation in humans.

Xiong, Ziyi; Dankova, Gabriela; Howe, Laurence J; Lee, Myoung Keun; Hysi, Pirro G; de Jong, Markus A; Zhu, Gu; Adhikari, Kaustubh et al. · Elife · 2019

basic_science · Level V

Where this comes from

Abstract

The human face represents a combined set of highly heritable phenotypes, but knowledge on its genetic architecture remains limited, despite the relevance for various fields. A series of genome-wide association studies on 78 facial shape phenotypes quantified from 3-dimensional facial images of 10,115 Europeans identified 24 genetic loci reaching study-wide suggestive association (p < 5 × 10<sup>-8</sup>), among which 17 were previously unreported. A follow-up multi-ethnic study in additional 7917 individuals confirmed 10 loci including six unreported ones (p<sub>adjusted</sub> < 2.1 × 10<sup>-3</sup>). A global map of derived polygenic face scores assembled facial features in major continental groups consistent with anthropological knowledge. Analyses of epigenomic datasets from cranial neural crest cells revealed abundant <i>cis</i>-regulatory activities at the face-associated genetic loci. Luciferase reporter assays in neural crest progenitor cells highlighted enhancer activities of several face-associated DNA variants. These results substantially advance our understanding of the genetic basis underlying human facial variation and provide candidates for future in-vivo functional studies.

Medical subject headings