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Artigo Acesso aberto Produção Nacional
BIBTEX RIS

Novel Genetic Loci Affecting Facial Shape Variation in Humans

2018; RELX Group (Netherlands); Linguagem: Inglês

10.2139/ssrn.3307375

ISSN

1556-5068

Autores

Ziyi Xiong, Haibo Zhou, Gabriela Dankova, Laurence J Howe, Myoung Keun Lee, Pirro G. Hysi, Markus A. de Jong, Gu Zhu, Kaustubh Adhikari, Dan Li, Yi Li, Li He, 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, Erwei Zuo, 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, Hui Yang, Timothy D. Spector, Evie Stergiakouli, Seth M. Weinberg, Fan Liu, Manfred Kayser,

Tópico(s)

Cleft Lip and Palate Research

Resumo

The human face represents a combined set of highly heritable phenotypes, but knowledge on its genetic architecture remains limited. 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from 3-dimensional facial images of 10,115 Europeans identified 24 genetic loci, among which 17 were previously unpublished. A multi-ethnic replication study in 7,917 individuals confirmed 13 loci including 8 unpublished ones. Allele frequencies at the face-associated loci were significantly more differentiated among populations than genome background, supporting a role of nature selection in shaping genetic differentiation underlying facial variation. Analyses of epigenomic datasets from cranial neural crest cells revealed abundant cis-regulatory activities at the face-associated loci. Luciferase reporter assays in neural crest progenitor cells highlighted enhancer activities at INTU, PAX3, RPGRIP1L. Knocking-out two face-associated genes TBX15 and PAX1 in mice resulted in craniofacial dysmorphology. These results substantially advance our understanding of the genetic and functional basis of human facial variation.

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