Shared heritability of human face and brain shape

Nat Genet. 2021 Jun;53(6):830-839. doi: 10.1038/s41588-021-00827-w. | PubMed

Sahin Naqvi^1,2, Yoeri Sleyp³, Hanne Hoskens^3,4, Karlijne Indencleef^4,5, Jeffrey P Spence⁶, Rose Bruffaerts^7,8,9, Ahmed Radwan^4,10, Ryan J Eller¹¹, Stephen Richmond¹², Mark D Shriver¹³, John R Shaffer^14,15, Seth M Weinberg^14,15,16, Susan Walsh¹¹, James Thompson¹⁷, Jonathan K Pritchard⁶, Stefan Sunaert^4,10, Hilde Peeters³, Joanna Wysocka^18,19,20, Peter Claes^21,22,23,24

1. Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA, USA. naqvi@stanford.edu.
2. Departments of Genetics and Biology, Stanford University School of Medicine, Stanford, CA, USA. naqvi@stanford.edu.
3. Department of Human Genetics, KU Leuven, Leuven, Belgium.
4. Medical Imaging Research Center, University Hospitals Leuven, Leuven, Belgium.
5. Department of Electrical Engineering, ESAT/PSI, KU Leuven, Leuven, Belgium.
6. Departments of Genetics and Biology, Stanford University School of Medicine, Stanford, CA, USA.
7. Department of Neurosciences, KU Leuven, Leuven, Belgium, Hasselt University, Hasselt, Belgium.
8. Neurology Department, University Hospitals Leuven, Leuven, Belgium, Hasselt University, Hasselt, Belgium.
9. Biomedical Research Institute Hasselt University Hasselt Belgium, Hasselt University, Hasselt, Belgium.
10. Department of Imaging and Pathology, Translational MRI, KU Leuven, Leuven, Belgium.
11. Department of Biology, Indiana University Purdue University Indianapolis, Indianapolis, IN, USA.
12. Applied Clinical Research and Public Health, School of Dentistry, Cardiff University, Cardiff, UK.
13. Department of Anthropology, Pennsylvania State University, State College, PA, USA.
14. Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA, USA.
15. Department of Oral and Craniofacial Sciences, Center for Craniofacial and Dental Genetics, University of Pittsburgh, Pittsburgh, PA, USA.
16. Department of Anthropology, University of Pittsburgh, Pittsburgh, PA, USA.
17. Department of Psychology, George Mason University, Fairfax, VA, USA.
18. Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA, USA. wysocka@stanford.edu.
19. Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA, USA. wysocka@stanford.edu.
20. Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA, USA. wysocka@stanford.edu.
21. Department of Human Genetics, KU Leuven, Leuven, Belgium. peter.claes@kuleuven.be.
22. Medical Imaging Research Center, University Hospitals Leuven, Leuven, Belgium. peter.claes@kuleuven.be.
23. Department of Electrical Engineering, ESAT/PSI, KU Leuven, Leuven, Belgium. peter.claes@kuleuven.be.
24. Murdoch Children's Research Institute, Melbourne, Victoria, Australia. peter.claes@kuleuven.be.

Abstract

Evidence from model organisms and clinical genetics suggests coordination between the developing brain and face, but the role of this link in common genetic variation remains unknown. We performed a multivariate genome-wide association study of cortical surface morphology in 19,644 individuals of European ancestry, identifying 472 genomic loci influencing brain shape, of which 76 are also linked to face shape. Shared loci include transcription factors involved in craniofacial development, as well as members of signaling pathways implicated in brain-face cross-talk. Brain shape heritability is equivalently enriched near regulatory regions active in either forebrain organoids or facial progenitors. However, we do not detect significant overlap between shared brain-face genome-wide association study signals and variants affecting behavioral-cognitive traits. These results suggest that early in embryogenesis, the face and brain mutually shape each other through both structural effects and paracrine signaling, but this interplay may not impact later brain development associated with cognitive function.

Presented By Sahin Naqvi | ORCID iD