Joint multi-ancestry and admixed GWAS reveals the complex genetics behind human cranial vault shape

Seppe Goovaerts; Hanne Hoskens; Ryan J. Eller; Noah Herrick; Anthony M. Musolf; Cristina M. Justice; Meng Yuan; Sahin Naqvi; Myoung Keun Lee; Dirk Vandermeulen; Heather L. Szabo-Rogers; Paul A. Romitti; Simeon A. Boyadjiev; Mary L. Marazita; John R. Shaffer; Mark D. Shriver; Joanna Wysocka; Susan Walsh; Seth M. Weinberg; Peter Claes

doi:10.1038/s41467-023-43237-8

Joint multi-ancestry and admixed GWAS reveals the complex genetics behind human cranial vault shape

Seppe Goovaerts, Hanne Hoskens, Ryan J. Eller, Noah Herrick, Anthony M. Musolf, Cristina M. Justice, Meng Yuan, Sahin Naqvi, Myoung Keun Lee, Dirk Vandermeulen, Heather L. Szabo-Rogers, Paul A. Romitti, Simeon A. Boyadjiev, Mary L. Marazita, John R. Shaffer, Mark D. Shriver, Joanna Wysocka, Susan Walsh, Seth M. Weinberg, Peter Claes

Anthropology

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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.

Original language	English (US)
Article number	7436
Journal	Nature communications
Volume	14
Issue number	1
DOIs	https://doi.org/10.1038/s41467-023-43237-8
State	Published - Dec 2023

All Science Journal Classification (ASJC) codes

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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Goovaerts, S., Hoskens, H., Eller, R. J., Herrick, N., Musolf, A. M., Justice, C. M., Yuan, M., Naqvi, S., Lee, M. K., Vandermeulen, D., Szabo-Rogers, H. L., Romitti, P. A., Boyadjiev, S. A., Marazita, M. L., Shaffer, J. R., Shriver, M. D., Wysocka, J., Walsh, S., Weinberg, S. M., & Claes, P. (2023). Joint multi-ancestry and admixed GWAS reveals the complex genetics behind human cranial vault shape. Nature communications, 14(1), Article 7436. https://doi.org/10.1038/s41467-023-43237-8

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title = "Joint multi-ancestry and admixed GWAS reveals the complex genetics behind human cranial vault shape",

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.",

author = "Seppe Goovaerts and Hanne Hoskens and Eller, {Ryan J.} and Noah Herrick and Musolf, {Anthony M.} and Justice, {Cristina M.} and Meng Yuan and Sahin Naqvi and Lee, {Myoung Keun} and Dirk Vandermeulen and Szabo-Rogers, {Heather L.} and Romitti, {Paul A.} and Boyadjiev, {Simeon A.} and Marazita, {Mary L.} and Shaffer, {John R.} and Shriver, {Mark D.} and Joanna Wysocka and Susan Walsh and Weinberg, {Seth M.} and Peter Claes",

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year = "2023",

month = dec,

doi = "10.1038/s41467-023-43237-8",

language = "English (US)",

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Goovaerts, S, Hoskens, H, Eller, RJ, Herrick, N, Musolf, AM, Justice, CM, Yuan, M, Naqvi, S, Lee, MK, Vandermeulen, D, Szabo-Rogers, HL, Romitti, PA, Boyadjiev, SA, Marazita, ML, Shaffer, JR, Shriver, MD, Wysocka, J, Walsh, S, Weinberg, SM & Claes, P 2023, 'Joint multi-ancestry and admixed GWAS reveals the complex genetics behind human cranial vault shape', Nature communications, vol. 14, no. 1, 7436. https://doi.org/10.1038/s41467-023-43237-8

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AU - Goovaerts, Seppe

AU - Hoskens, Hanne

AU - Eller, Ryan J.

AU - Herrick, Noah

AU - Musolf, Anthony M.

AU - Justice, Cristina M.

AU - Yuan, Meng

AU - Naqvi, Sahin

AU - Lee, Myoung Keun

AU - Vandermeulen, Dirk

AU - Szabo-Rogers, Heather L.

AU - Romitti, Paul A.

AU - Boyadjiev, Simeon A.

AU - Marazita, Mary L.

AU - Shaffer, John R.

AU - Shriver, Mark D.

AU - Wysocka, Joanna

AU - Walsh, Susan

AU - Weinberg, Seth M.

AU - Claes, Peter

PY - 2023/12

Y1 - 2023/12

N2 - 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.

AB - 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.

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Joint multi-ancestry and admixed GWAS reveals the complex genetics behind human cranial vault shape

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