Journal article
Joint multi-ancestry and admixed GWAS reveals the complex genetics behind human cranial vault shape
Nature communications, Vol.14(1), 7436
11/16/2023
DOI: 10.1038/s41467-023-43237-8
PMCID: PMC10654897
PMID: 37973980
Abstract
The cranial vault in humans is highly variable, clinically relevant, and heritable, yet its genetic architecture remains poorly understood. Here, we conduct a joint multi-ancestry and admixed multivariate genome-wide association study on 3D cranial vault shape extracted from magnetic resonance images of 6772 children from the ABCD study cohort yielding 30 genome-wide significant loci. Follow-up analyses indicate that these loci overlap with genomic risk loci for sagittal craniosynostosis, show elevated activity cranial neural crest cells, are enriched for processes related to skeletal development, and are shared with the face and brain. We present supporting evidence of regional localization for several of the identified genes based on expression patterns in the cranial vault bones of E15.5 mice. Overall, our study provides a comprehensive overview of the genetics underlying normal-range cranial vault shape and its relevance for understanding modern human craniofacial diversity and the etiology of congenital malformations.
Details
- Title: Subtitle
- Joint multi-ancestry and admixed GWAS reveals the complex genetics behind human cranial vault shape
- Creators
- Seppe Goovaerts - KU LeuvenHanne Hoskens - KU LeuvenRyan J Eller - Indiana University – Purdue University IndianapolisNoah Herrick - Indiana University – Purdue University IndianapolisAnthony M Musolf - National Human Genome Research InstituteCristina M Justice - National Human Genome Research InstituteMeng Yuan - KU LeuvenSahin Naqvi - Stanford UniversityMyoung Keun Lee - University of PittsburghDirk Vandermeulen - KU LeuvenHeather L Szabo-Rogers - University of SaskatchewanPaul A Romitti - University of IowaSimeon A Boyadjiev - University of California, DavisMary L Marazita - University of PittsburghJohn R Shaffer - University of PittsburghMark D Shriver - Pennsylvania State UniversityJoanna Wysocka - Stanford UniversitySusan Walsh - Indiana University – Purdue University IndianapolisSeth M Weinberg - University of PittsburghPeter Claes - KU Leuven
- Resource Type
- Journal article
- Publication Details
- Nature communications, Vol.14(1), 7436
- DOI
- 10.1038/s41467-023-43237-8
- PMID
- 37973980
- PMCID
- PMC10654897
- NLM abbreviation
- Nat Commun
- eISSN
- 2041-1723
- Grant note
- DOI: 10.13039/100000072, name: U.S. Department of Health & Human Services | NIH | National Institute of Dental and Craniofacial Research, award: R01DE027023, K99DE032729, R01DE016886, R01DE016886, R03DE031061, X01HL14053, R01DE027023, R01DE027023, R01DE027023, R01DE027023, R01DE027023; name: U.S. Department of Health & Human Services | NIH | National Institute of Dental and Craniofacial Research; name: U.S. Department of Health & Human Services | NIH | National Institute of Dental and Craniofacial Research; name: U.S. Department of Health & Human Services | NIH | National Institute of Dental and Craniofacial Research; name: U.S. Department of Health & Human Services | NIH | National Institute of Dental and Craniofacial Research; name: U.S. Department of Health & Human Services | NIH | National Institute of Dental and Craniofacial Research; name: U.S. Department of Health & Human Services | NIH | National Institute of Dental and Craniofacial Research; name: U.S. Department of Health & Human Services | NIH | National Institute of Dental and Craniofacial Research; name: U.S. Department of Health & Human Services | NIH | National Institute of Dental and Craniofacial Research; name: U.S. Department of Health & Human Services | NIH | National Institute of Dental and Craniofacial Research; name: U.S. Department of Health & Human Services | NIH | National Institute of Dental and Craniofacial Research
- Language
- English
- Date published
- 11/16/2023
- Academic Unit
- Epidemiology; Biostatistics
- Record Identifier
- 9984513300802771
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