Novel genetic loci affecting facial shape variation in humans.

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Novel genetic loci affecting facial shape variation in humans.

Elife. 2019 11 26;8:

Authors: Xiong Z, Dankova G, Howe LJ, Lee MK, Hysi PG, de Jong MA, Zhu G, Adhikari K, Li D, Li Y, Pan B, Feingold E, Marazita ML, Shaffer JR, McAloney K, Xu SH, Jin L, Wang S, de Vrij FM, Lendemeijer B, Richmond S, Zhurov A, Lewis S, Sharp GC, Paternoster L, Thompson H, Gonzalez-Jose R, Bortolini MC, Canizales-Quinteros S, Gallo C, Poletti G, Bedoya G, Rothhammer F, Uitterlinden AG, Ikram MA, Wolvius E, Kushner SA, Nijsten TE, Palstra RT, Boehringer S, Medland SE, Tang K, Ruiz-Linares A, Martin NG, Spector TD, Stergiakouli E, Weinberg SM, Liu F, Kayser M, International Visible Trait Genetics (VisiGen) Consortium

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.

PMID: 31763980 [PubMed – indexed for MEDLINE]