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Genome-wide association meta-analysis of age at onset of walking in over 70,000 infants of European ancestry

Author

Listed:
  • Anna Gui

    (Wivenhoe Park
    Birkbeck University of London)

  • Anja Hollowell

    (Birkbeck University of London)

  • Emilie M. Wigdor

    (University of Oxford)

  • Morgan J. Morgan

    (Guildford)

  • Laurie J. Hannigan

    (Lovisenberg Diaconal Hospital
    Norwegian Institute of Public Health
    University of Bristol)

  • Elizabeth C. Corfield

    (Lovisenberg Diaconal Hospital
    Norwegian Institute of Public Health)

  • Veronika Odintsova

    (Vrije Universiteit Amsterdam
    University of Groningen)

  • Jouke-Jan Hottenga

    (Vrije Universiteit Amsterdam)

  • Andrew Wong

    (University College London)

  • René Pool

    (Vrije Universiteit Amsterdam)

  • Harriet Cullen

    (King’s College London
    King’s College London)

  • Siân Wilson

    (Boston Children’s Hospital
    Harvard Medical School)

  • Varun Warrier

    (University of Cambridge)

  • Espen M. Eilertsen

    (University of Oslo)

  • Ole A. Andreassen

    (University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital
    University of Oslo)

  • Christel M. Middeldorp

    (Amsterdam UMC
    Arkin Mental Health Care
    Levvel, Academic Center for Child and Adolescent Psychiatry
    University of Queensland)

  • Beate St Pourcain

    (Max Planck Institute for Psycholinguistics
    University of Bristol
    Radboud University)

  • Meike Bartels

    (Vrije Universiteit Amsterdam)

  • Dorret I. Boomsma

    (Vrije Universiteit)

  • Catharina A. Hartman

    (University of Groningen)

  • Elise B. Robinson

    (Broad Institute)

  • Tomoki Arichi

    (King’s College London)

  • Anthony D. Edwards

    (King’s College London)

  • Mark H. Johnson

    (Birkbeck University of London
    University of Cambridge)

  • Frank Dudbridge

    (University of Leicester)

  • Stephan J. Sanders

    (University of Oxford
    University of California)

  • Alexandra Havdahl

    (Lovisenberg Diaconal Hospital
    Norwegian Institute of Public Health
    University of Oslo)

  • Angelica Ronald

    (Birkbeck University of London
    Guildford)

Abstract

Age at onset of walking is an important early childhood milestone which is used clinically and in public health screening. In this genome-wide association study meta-analysis of age at onset of walking (N = 70,560 European-ancestry infants), we identified 11 independent genome-wide significant loci. SNP-based heritability was 24.13% (95% confidence intervals = 21.86–26.40) with ~11,900 variants accounting for about 90% of it, suggesting high polygenicity. One of these loci, in gene RBL2, co-localized with an expression quantitative trait locus (eQTL) in the brain. Age at onset of walking (in months) was negatively genetically correlated with ADHD and body-mass index, and positively genetically correlated with brain gyrification in both infant and adult brains. The polygenic score showed out-of-sample prediction of 3–5.6%, confirmed as largely due to direct effects in sib-pair analyses, and was separately associated with volume of neonatal brain structures involved in motor control. This study offers biological insights into a key behavioural marker of neurodevelopment.

Suggested Citation

  • Anna Gui & Anja Hollowell & Emilie M. Wigdor & Morgan J. Morgan & Laurie J. Hannigan & Elizabeth C. Corfield & Veronika Odintsova & Jouke-Jan Hottenga & Andrew Wong & René Pool & Harriet Cullen & Siân, 2025. "Genome-wide association meta-analysis of age at onset of walking in over 70,000 infants of European ancestry," Nature Human Behaviour, Nature, vol. 9(7), pages 1470-1487, July.
    • Handle: RePEc:nat:nathum:v:9:y:2025:i:7:d:10.1038_s41562-025-02145-1
    DOI: 10.1038/s41562-025-02145-1
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