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

Author

Listed:
  • Seppe Goovaerts

    (KU Leuven
    University Hospitals Leuven)

  • Hanne Hoskens

    (University Hospitals Leuven
    KU Leuven)

  • Ryan J. Eller

    (Indiana University Indianapolis)

  • Noah Herrick

    (Indiana University Indianapolis)

  • Anthony M. Musolf

    (Statistical Genetics Section, Computational and Statistical Genomics Branch, NHGRI, NIH, MD)

  • Cristina M. Justice

    (Genometrics Section, Computational and Statistical Genomics Branch, Division of Intramural Research, NHGRI, NIH
    National Institutes of Health)

  • Meng Yuan

    (KU Leuven
    University Hospitals Leuven
    KU Leuven)

  • Sahin Naqvi

    (Stanford University School of Medicine
    Stanford University School of Medicine)

  • Myoung Keun Lee

    (University of Pittsburgh)

  • Dirk Vandermeulen

    (University Hospitals Leuven
    KU Leuven)

  • Heather L. Szabo-Rogers

    (University of Saskatchewan)

  • Paul A. Romitti

    (The University of Iowa)

  • Simeon A. Boyadjiev

    (University of California Davis)

  • Mary L. Marazita

    (University of Pittsburgh
    University of Pittsburgh)

  • John R. Shaffer

    (University of Pittsburgh
    University of Pittsburgh)

  • Mark D. Shriver

    (Pennsylvania State University)

  • Joanna Wysocka

    (Stanford University School of Medicine
    Stanford University School of Medicine
    Stanford University School of Medicine)

  • Susan Walsh

    (Indiana University Indianapolis)

  • Seth M. Weinberg

    (University of Pittsburgh
    University of Pittsburgh
    University of Pittsburgh)

  • Peter Claes

    (KU Leuven
    University Hospitals Leuven
    KU Leuven
    Murdoch Children’s Research Institute)

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.

Suggested Citation

  • 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 & Pau, 2023. "Joint multi-ancestry and admixed GWAS reveals the complex genetics behind human cranial vault shape," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43237-8
    DOI: 10.1038/s41467-023-43237-8
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