학술논문
Novel genetic loci affecting facial shape variation in humans
Document Type
article
Author
Ziyi Xiong; Gabriela Dankova; Laurence J Howe; Myoung Keun Lee; Pirro G Hysi; Markus A de Jong; Gu Zhu; Kaustubh Adhikari; Dan Li; Yi Li; Bo Pan; Eleanor Feingold; Mary L Marazita; John R Shaffer; Kerrie McAloney; Shu-Hua Xu; Li Jin; Sijia Wang; Femke MS de Vrij; Bas Lendemeijer; Stephen Richmond; Alexei Zhurov; Sarah Lewis; Gemma C Sharp; Lavinia Paternoster; Holly Thompson; Rolando Gonzalez-Jose; Maria Catira Bortolini; Samuel Canizales-Quinteros; Carla Gallo; Giovanni Poletti; Gabriel Bedoya; Francisco Rothhammer; André G Uitterlinden; M Arfan Ikram; Eppo Wolvius; Steven A Kushner; Tamar EC Nijsten; Robert-Jan TS Palstra; Stefan Boehringer; Sarah E Medland; Kun Tang; Andres Ruiz-Linares; Nicholas G Martin; Timothy D Spector; Evie Stergiakouli; Seth M Weinberg; Fan Liu; Manfred Kayser; On behalf of the International Visible Trait Genetics (VisiGen) Consortium
Source
eLife, Vol 8 (2019)
Subject
Language
English
ISSN
2050-084X
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 × 10−8), among which 17 were previously unreported. A follow-up multi-ethnic study in additional 7917 individuals confirmed 10 loci including six unreported ones (padjusted < 2.1 × 10−3). 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 cis-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.