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

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 Wilson, Varun Warrier, Espen M. Eilertsen, Ole A. Andreassen, Christel M. Middeldorp, Beate St Pourcain, Meike Bartels, Dorret I. Boomsma, Catharina A. Hartman, Elise B. Robinson, Tomoki Arichi, Anthony D. Edwards, Mark H. Johnson, Frank Dudbridge, Stephan J. Sanders, Alexandra Havdahl and Angelica Ronald ()
Additional contact information
Anna Gui: Wivenhoe Park
Anja Hollowell: Birkbeck University of London
Emilie M. Wigdor: University of Oxford
Morgan J. Morgan: Guildford
Laurie J. Hannigan: Lovisenberg Diaconal Hospital
Elizabeth C. Corfield: Lovisenberg Diaconal Hospital
Veronika Odintsova: Vrije Universiteit Amsterdam
Jouke-Jan Hottenga: Vrije Universiteit Amsterdam
Andrew Wong: University College London
René Pool: Vrije Universiteit Amsterdam
Harriet Cullen: King’s College London
Siân Wilson: Boston Children’s Hospital
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
Christel M. Middeldorp: Amsterdam UMC
Beate St Pourcain: Max Planck Institute for Psycholinguistics
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
Frank Dudbridge: University of Leicester
Stephan J. Sanders: University of Oxford
Alexandra Havdahl: Lovisenberg Diaconal Hospital
Angelica Ronald: Birkbeck University of London

Nature Human Behaviour, 2025, vol. 9, issue 7, 1470-1487

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41562-025-02145-1

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