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Novel genetic loci affecting facial shape variation in humans

2019; eLife Sciences Publications Ltd; Volume: 8; Linguagem: Inglês

10.7554/elife.49898

2050-084X

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, Shuhua Xu, Jin Li, Sijia Wang, Femke M.S. de Vrij, Bas Lendemeijer, Stephen Richmond, Alexei I. Zhurov, Sarah J. Lewis, Gemma C. Sharp, Lavinia Paternoster, Holly Thompson, Rolando González‐José, María Cátira Bortolini, Samuel Canizales‐Quinteros, Carla Gallo, Giovanni Poletti, Gabriel Bedoya, Francisco Rothhammer, André G. Uitterlinden, M. Arfan Ikram, Eppo B. Wolvius, Steven A. Kushner, Tamar Nijsten, Robert‐Jan Palstra, Stefan Böehringer, Sarah E. Medland, Kun Tang, Andrés Ruiz‐Linares, Nicholas G. Martin, Timothy D. Spector, Evie Stergiakouli, Seth M. Weinberg, Fan Liu, Manfred Kayser,

Morphological variations and asymmetry

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.