Insights into the genetic architecture of the human face

Julie D. White; Karlijne Indencleef; Sahin Naqvi; Ryan Jospeh Eller; Hanne Hoskens; Jasmien Roosenboom; Myoung Keun Lee; Jiarui Li; Jaaved Mohammed; Stephen Richmond; Ellen E. Quillen; Heather Norton; Eleanor Feingold; Tomek Swigut; Mary L. Marazita; Hilde Peeters; Greet Hens; John R. Shaffer; Joanna Wysocka; Susan Walsh; Seth Michael Weinberg; Mark D. Shriver; Peter D. Claes

doi:10.1038/s41588-020-00741-7

GeneticsNature GeneticsDec 7, 2020

Peer-reviewed journal article

Insights into the genetic architecture of the human face

Julie D. White iD, Karlijne Indencleef iD, Sahin Naqvi iD, Ryan Jospeh Eller iD, Hanne Hoskens iD, Jasmien Roosenboom iD, Myoung Keun Lee iD, Jiarui Li iD, Jaaved Mohammed iD, Stephen Richmond iD, Ellen E. Quillen iD, Heather Norton iD, Eleanor Feingold iD, Tomek Swigut iD, Mary L. Marazita iD, Hilde Peeters iD, Greet Hens iD, John R. Shaffer iD, Joanna Wysocka iD, Susan Walsh iD, Seth Michael Weinberg iD, Mark D. Shriver iD, Peter D. Claes iD

Abstract

The human face is complex and multipartite, and characterization of its genetic architecture remains intriguingly challenging. Applying GWAS to multivariate shape phenotypes, we identified 203 genomic regions associated with normal-range facial variation, 117 of which are novel. The associated regions are enriched for both genes relevant to craniofacial and limb morphogenesis and enhancer activity in cranial neural crest cells and craniofacial tissues. Genetic variants grouped by their contribution to similar aspects of facial variation show high within-group correlation of enhancer activity, and four SNP pairs display evidence of epistasis, indicating potentially coordinated actions of variants within the same cell types or tissues. In sum, our analyses provide new insights for understanding how complex morphological traits are shaped by both individual and coordinated genetic actions.

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