Low-frequency variation in TP53 has large effects on head circumference and intracranial volume View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

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 Guxens, Jordi Sunyer, Ioanna Tachmazidou, Klaudia Walter, Valentina Iotchkova, Andrew Jackson, Louise Cleal, Jennifer Huffmann, Josine L. Min, Lærke Sass, Paul R. H. J. Timmers, , George Davey Smith, Simon E. Fisher, James F. Wilson, Tim J. Cole, Dietmar Fernandez-Orth, Klaus Bønnelykke, Hans Bisgaard, Craig E. Pennell, Vincent W. V. Jaddoe, George Dedoussis, Nicholas Timpson, Eleftheria Zeggini, Veronique Vitart, Beate St Pourcain

ABSTRACT

Cranial growth and development is a complex process which affects the closely related traits of head circumference (HC) and intracranial volume (ICV). The underlying genetic influences shaping these traits during the transition from childhood to adulthood are little understood, but might include both age-specific genetic factors and low-frequency genetic variation. Here, we model the developmental genetic architecture of HC, showing this is genetically stable and correlated with genetic determinants of ICV. Investigating up to 46,000 children and adults of European descent, we identify association with final HC and/or final ICV + HC at 9 novel common and low-frequency loci, illustrating that genetic variation from a wide allele frequency spectrum contributes to cranial growth. The largest effects are reported for low-frequency variants within TP53, with 0.5 cm wider heads in increaser-allele carriers versus non-carriers during mid-childhood, suggesting a previously unrecognized role of TP53 transcripts in human cranial development. More... »

PAGES

357

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41467-018-07863-x

    DOI

    http://dx.doi.org/10.1038/s41467-018-07863-x

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1111563907

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30664637


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