Nat Genet. 2018 Mar;50(3):414-423. doi: 10.1038/s41588-018-0057-4. Epub 2018 Feb 19.

Genome-wide mapping of global-to-local genetic effects on human facial shape.

Claes P^1,^2,³, Roosenboom J⁴, White JD⁵, Swigut T⁶, Sero D^7,⁸, Li J^7,⁸, Lee MK⁴, Zaidi A⁵, Mattern BC⁵, Liebowitz C⁵, Pearson L⁵, González T⁵, Leslie EJ⁴, Carlson JC⁹, Orlova E¹⁰, Suetens P^7,⁸, Vandermeulen D^7,⁸, Feingold E^9,¹⁰, Marazita ML^4,¹⁰, Shaffer JR¹⁰, Wysocka J^11,¹², Shriver MD¹³, Weinberg SM^14,¹⁵.

Author information

1: Department of Electrical Engineering, ESAT/PSI, KU Leuven, Leuven, Belgium. peter.claes@kuleuven.be.
2: Medical Imaging Research Center, MIRC, UZ Leuven, Leuven, Belgium. peter.claes@kuleuven.be.
3: Murdoch Childrens Research Institute, Melbourne, Victoria, Australia. peter.claes@kuleuven.be.
4: Center for Craniofacial and Dental Genetics, Department of Oral Biology, University of Pittsburgh, Pittsburgh, PA, USA.
5: Department of Anthropology, Penn State University, University Park, PA, USA.
6: Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA, USA.
7: Department of Electrical Engineering, ESAT/PSI, KU Leuven, Leuven, Belgium.
8: Medical Imaging Research Center, MIRC, UZ Leuven, Leuven, Belgium.
9: Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA, USA.
10: Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA, USA.
11: Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA, USA. wysocka@stanford.edu.
12: Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA, USA. wysocka@stanford.edu.
13: Department of Anthropology, Penn State University, University Park, PA, USA. mds17@psu.edu.
14: Center for Craniofacial and Dental Genetics, Department of Oral Biology, University of Pittsburgh, Pittsburgh, PA, USA. smwst46@pitt.edu.
15: Department of Anthropology, University of Pittsburgh, Pittsburgh, PA, USA. smwst46@pitt.edu.

Abstract

Genome-wide association scans of complex multipartite traits like the human face typically use preselected phenotypic measures. Here we report a data-driven approach to phenotyping facial shape at multiple levels of organization, allowing for an open-ended description of facial variation while preserving statistical power. In a sample of 2,329 persons of European ancestry, we identified 38 loci, 15 of which replicated in an independent European sample (n = 1,719). Four loci were completely new. For the others, additional support (n = 9) or pleiotropic effects (n = 2) were found in the literature, but the results reported here were further refined. All 15 replicated loci highlighted distinctive patterns of global-to-local genetic effects on facial shape and showed enrichment for active chromatin elements in human cranial neural crest cells, suggesting an early developmental origin of the facial variation captured. These results have implications for studies of facial genetics and other complex morphological traits.