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eLife Volume 8 ,2019-11-22
Novel genetic loci affecting facial shape variation in humans
Genetics and Genomics
Ziyi Xiong 1 , 2 , 3 Gabriela Dankova 1 Laurence J Howe 4 Myoung Keun Lee 5 Pirro G Hysi 6 Markus A de Jong 1 , 7 , 8 Gu Zhu 9 Kaustubh Adhikari 10 Dan Li 11 , 12 , 13 Yi Li 3 Bo Pan 14 Eleanor Feingold 5 Mary L Marazita 5 , 15 John R Shaffer 5 , 15 Kerrie McAloney 9 Shu-Hua Xu 11 , 12 , 13 , 16 , 17 Li Jin 11 , 12 , 13 , 18 , 19 Sijia Wang 11 , 12 , 13 , 17 Femke MS de Vrij 20 Bas Lendemeijer 20 Stephen Richmond 21 Alexei Zhurov 21 Sarah Lewis 4 Gemma C Sharp 4 , 22 Lavinia Paternoster 4 Holly Thompson 4 Rolando Gonzalez-Jose 23 Maria Catira Bortolini 24 Samuel Canizales-Quinteros 25 Carla Gallo 26 Giovanni Poletti 26 Gabriel Bedoya 27 Francisco Rothhammer 28 André G Uitterlinden 2 , 29 M Arfan Ikram 2 Eppo Wolvius 7 Steven A Kushner 20 Tamar EC Nijsten 30 Robert-Jan TS Palstra 31 Stefan Boehringer 8 Sarah E Medland 9 Kun Tang 11 , 12 , 13 Andres Ruiz-Linares 18 , 19 , 32 Nicholas G Martin 9 Timothy D Spector 6 Evie Stergiakouli 4 , 22 Seth M Weinberg 5 , 15 , 33 Fan Liu 1 , 3 Manfred Kayser 1
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DOI:10.7554/eLife.49898
Received 2019-07-03, accepted for publication 2019-11-22, Published 2019-11-22
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摘要

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.

关键词

Human;GWAS;images;gene regulation;European;face;genome-wide association study

授权许可

© 2019, Xiong et al
http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.

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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. Novel genetic loci affecting facial shape variation in humans. eLife ,Vol.8(2019)

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