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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.

SUBMITTER: Goovaerts S

PROVIDER: S-EPMC10654897 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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

Goovaerts Seppe S Hoskens Hanne H Eller Ryan J RJ Herrick Noah N Musolf Anthony M AM Justice Cristina M CM Yuan Meng M Naqvi Sahin S Lee Myoung Keun MK Vandermeulen Dirk D Szabo-Rogers Heather L HL Romitti Paul A PA Boyadjiev Simeon A SA Marazita Mary L ML Shaffer John R JR Shriver Mark D MD Wysocka Joanna J Walsh Susan S Weinberg Seth M SM Claes Peter P

Nature communications 20231116 1

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 e ...[more]

PMID: 37973980

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

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

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