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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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    as
    1. Claudia Giambartolomei & Damjan Vukcevic & Eric E Schadt & Lude Franke & Aroon D Hingorani & Chris Wallace & Vincent Plagnol, 2014. "Bayesian Test for Colocalisation between Pairs of Genetic Association Studies Using Summary Statistics," PLOS Genetics, Public Library of Science, vol. 10(5), pages 1-15, May.
    2. Simone Rubinacci & Olivier Delaneau & Jonathan Marchini, 2020. "Genotype imputation using the Positional Burrows Wheeler Transform," PLOS Genetics, Public Library of Science, vol. 16(11), pages 1-19, November.
    3. Olivier Delaneau & Jean-François Zagury & Matthew R. Robinson & Jonathan L. Marchini & Emmanouil T. Dermitzakis, 2019. "Accurate, scalable and integrative haplotype estimation," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
    4. Jing Guo & Yang Wu & Zhihong Zhu & Zhili Zheng & Maciej Trzaskowski & Jian Zeng & Matthew R. Robinson & Peter M. Visscher & Jian Yang, 2018. "Global genetic differentiation of complex traits shaped by natural selection in humans," Nature Communications, Nature, vol. 9(1), pages 1-9, December.
    5. Jasmien Roosenboom & Myoung Keun Lee & Jacqueline T Hecht & Carrie L Heike & George L Wehby & Kaare Christensen & Eleanor Feingold & Mary L Marazita & A Murat Maga & John R Shaffer & Seth M Weinberg, 2018. "Mapping genetic variants for cranial vault shape in humans," PLOS ONE, Public Library of Science, vol. 13(4), pages 1-14, April.
    6. Clare Bycroft & Colin Freeman & Desislava Petkova & Gavin Band & Lloyd T. Elliott & Kevin Sharp & Allan Motyer & Damjan Vukcevic & Olivier Delaneau & Jared O’Connell & Adrian Cortes & Samantha Welsh &, 2018. "The UK Biobank resource with deep phenotyping and genomic data," Nature, Nature, vol. 562(7726), pages 203-209, October.
    7. Kyoko Watanabe & Erdogan Taskesen & Arjen Bochoven & Danielle Posthuma, 2017. "Functional mapping and annotation of genetic associations with FUMA," Nature Communications, Nature, vol. 8(1), pages 1-11, December.
    8. Simon Haworth & Chin Yang Shapland & Caroline Hayward & Bram P. Prins & Janine F. Felix & Carolina Medina-Gomez & Fernando Rivadeneira & Carol Wang & Tarunveer S. Ahluwalia & Martine Vrijheid & Mònica, 2019. "Low-frequency variation in TP53 has large effects on head circumference and intracranial volume," Nature Communications, Nature, vol. 10(1), pages 1-16, December.
    9. Siddharth Menon & Ankit Salhotra & Siny Shailendra & Ruth Tevlin & Ryan C. Ransom & Michael Januszyk & Charles K. F. Chan & Björn Behr & Derrick C. Wan & Michael T. Longaker & Natalina Quarto, 2021. "Skeletal stem and progenitor cells maintain cranial suture patency and prevent craniosynostosis," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    10. Michael Lawrence & Wolfgang Huber & Hervé Pagès & Patrick Aboyoun & Marc Carlson & Robert Gentleman & Martin T Morgan & Vincent J Carey, 2013. "Software for Computing and Annotating Genomic Ranges," PLOS Computational Biology, Public Library of Science, vol. 9(8), pages 1-10, August.
    11. B. Devlin & Kathryn Roeder, 1999. "Genomic Control for Association Studies," Biometrics, The International Biometric Society, vol. 55(4), pages 997-1004, December.
    12. Thomas Gietzen & Robert Brylka & Jascha Achenbach & Katja zum Hebel & Elmar Schömer & Mario Botsch & Ulrich Schwanecke & Ralf Schulze, 2019. "A method for automatic forensic facial reconstruction based on dense statistics of soft tissue thickness," PLOS ONE, Public Library of Science, vol. 14(1), pages 1-19, January.
    13. Vania Broccoli & Edoardo Boncinelli & Wolfgang Wurst, 1999. "The caudal limit of Otx2 expression positions the isthmic organizer," Nature, Nature, vol. 401(6749), pages 164-168, September.
    14. Huber Wolfgang & von Heydebreck Anja & Sueltmann Holger & Poustka Annemarie & Vingron Martin, 2003. "Parameter estimation for the calibration and variance stabilization of microarray data," Statistical Applications in Genetics and Molecular Biology, De Gruyter, vol. 2(1), pages 1-24, April.
    15. D’Juan T. Farmer & Hana Mlcochova & Yan Zhou & Nils Koelling & Guanlin Wang & Neil Ashley & Helena Bugacov & Hung-Jhen Chen & Riana Parvez & Kuo-Chang Tseng & Amy E. Merrill & Robert E. Maxson & Andre, 2021. "The developing mouse coronal suture at single-cell resolution," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    16. Antonio Tedeschi & Jorge Almagro & Matthew J. Renshaw & Hendrik A. Messal & Axel Behrens & Mark Petronczki, 2020. "Cep55 promotes cytokinesis of neural progenitors but is dispensable for most mammalian cell divisions," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
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