Enhanced insights into the genetic architecture of 3D cranial vault shape using pleiotropy-informed GWAS
Large-scale GWAS studies have uncovered hundreds of genomic loci linked to facial and brain shape variation, but only tens associated with cranial vault shape, a largely overlooked aspect of the craniofacial complex. Surrounding the neocortex, the cranial vault plays a central role during craniofacial development and understanding its genetics are pivotal for understanding craniofacial conditions. Experimental biology and prior genetic studies have generated a wealth of knowledge that presents opportunities to aid further genetic discovery efforts. Here, we use the conditional FDR method to leverage GWAS data of facial shape, brain shape, and bone mineral density to enhance SNP discovery for cranial vault shape. This approach identified 120 independent genomic loci at 1% FDR, nearly tripling the number discovered through unconditioned analysis and implicating crucial craniofacial transcription factors and signaling pathways. These results significantly advance our genetic understanding of cranial vault shape and craniofacial development more broadly.
Authors
- Hanne Hoskens (ORCID: https://orcid.org/0000-0002-1467-6461)
- Seppe Goovaerts (ORCID: https://orcid.org/0000-0001-5176-8552)
- John R. Shaffer (ORCID: https://orcid.org/0000-0003-1897-1131)
- Seth M. Weinberg (ORCID: https://orcid.org/0000-0001-9467-4556)
- Peter D. Claes (ORCID: https://orcid.org/0000-0001-9489-9819)
- Mark D. Shriver (ORCID: https://orcid.org/0000-0003-0006-0479)
- Joanna Wysocka (ORCID: https://orcid.org/0000-0002-6909-6544)
- Noah Herrick (ORCID: https://orcid.org/0009-0004-3251-8311)
- Susan Walsh (ORCID: https://orcid.org/0000-0002-7064-1589)
- Meng Yuan (ORCID: https://orcid.org/0000-0003-0922-8012)
- Sahin Naqvi
Institutions
- Boston Children's Hospital (US)
- Pennsylvania State University (US)
- Howard Hughes Medical Institute (US)
- Harvard University (US)
- University of Pittsburgh (US)
- Alberta Children's Hospital (CA)
- Murdoch Children's Research Institute (AU)
- Indiana University Indianapolis (US)
- Indiana University – Purdue University Indianapolis (US)
- Stanford University (US)
- KU Leuven (BE)
Publication Details
- Journal
- Communications Biology
- Published
- 2025-03-15
- DOI
- https://doi.org/10.1038/s42003-025-07875-6
- Citations
- 1
- Primary Topic
- Morphological variations and asymmetry
- Type
- article
- Field-Weighted Citation Impact
- 4.09
Funders
- Vlaams Supercomputer Centrum
- Fonds Wetenschappelijk Onderzoek
- Vlaamse regering
- National Institutes of Health
- National Institute of Mental Health
- National Institute of Dental and Craniofacial Research