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; Angelica Ronald

doi:10.1038/s41562-025-02145-1

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

Nat Hum Behav. 2025 May 7. doi: 10.1038/s41562-025-02145-1. Online ahead of print.

Authors

Anna Gui^{1

2}, Anja Hollowell², Emilie M Wigdor³, Morgan J Morgan⁴, Laurie J Hannigan^{5

6

7}, Elizabeth C Corfield^{5

6}, Veronika Odintsova^{8

9}, Jouke-Jan Hottenga⁸, Andrew Wong¹⁰, René Pool⁸, Harriet Cullen^{11

12}, Siân Wilson^{13

14}, Varun Warrier¹⁵, Espen M Eilertsen¹⁶, Ole A Andreassen^{17

18}, Christel M Middeldorp^{19

20

21

22

23}, Beate St Pourcain^{24

25

26}, Meike Bartels⁸, Dorret I Boomsma²⁷, Catharina A Hartman²⁸, Elise B Robinson²⁹, Tomoki Arichi¹¹, Anthony D Edwards¹¹, Mark H Johnson^{2

30}, Frank Dudbridge³¹, Stephan J Sanders^#^{3

32}, Alexandra Havdahl^#^{5

6

16}, Angelica Ronald^#^{33

34}

Affiliations

¹ Department of Psychology, University of Essex, Wivenhoe Park, Colchester, UK.
² Centre for Brain and Cognitive Development, Department of Psychological Sciences, Birkbeck University of London, London, UK.
³ Institute of Developmental and Regenerative Medicine, Department of Paediatrics, University of Oxford, Oxford, UK.
⁴ School of Psychology, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, UK.
⁵ Research Department, Lovisenberg Diaconal Hospital, Oslo, Norway.
⁶ PsychGen Centre for Genetic Epidemiology and Mental Health, Norwegian Institute of Public Health, Oslo, Norway.
⁷ Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
⁸ Department of Biological Psychology, Faculty of Behavioral and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
⁹ Department of Psychiatry, University Medical Center of Groningen, University of Groningen, Groningen, the Netherlands.
¹⁰ MRC Unit for Lifelong Health and Ageing at UCL, University College London, London, UK.
¹¹ Research Department of Early Life Imaging, School of Biomedical Engineering and Imaging Sciences, King's College London, London, UK.
¹² Department of Medical and Molecular Genetics, School of Basic and Medical Biosciences, King's College London, London, UK.
¹³ Fetal-Neonatal Neuroimaging and Developmental Science Center, Boston Children's Hospital, Boston, MA, USA.
¹⁴ Division of Newborn Medicine, Harvard Medical School, Boston, MA, USA.
¹⁵ Department of Psychiatry and Psychology, University of Cambridge, Cambridge, UK.
¹⁶ PROMENTA Research Center, University of Oslo, Oslo, Norway.
¹⁷ Centre for Precision Psychiatry, Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
¹⁸ KG Jebsen Centre for Neurodevelopmental disorders, University of Oslo, Oslo, Norway.
¹⁹ Department of Child and Youth Psychiatry and Psychology, Amsterdam Reproduction and Development Research Institute, Amsterdam Public Health Research Institute, Amsterdam UMC, Amsterdam, the Netherlands.
²⁰ Arkin Mental Health Care, Amsterdam, the Netherlands.
²¹ Levvel, Academic Center for Child and Adolescent Psychiatry, Amsterdam, the Netherlands.
²² Child Health Research Centre, University of Queensland, Brisbane, Australia.
²³ Child and Youth Mental Health Service, Children's Health Queensland Hospital and Health Service, Brisbane, Australia.
²⁴ Max Planck Institute for Psycholinguistics, Nijmegen, the Netherlands.
²⁵ MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
²⁶ Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, the Netherlands.
²⁷ Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Vrije Universiteit, Amsterdam, the Netherlands.
²⁸ University Medical Center Psychopathology and Emotion Regulation (ICPE), Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
²⁹ Broad Institute, Boston, MA, USA.
³⁰ Department of Psychology, University of Cambridge, Cambridge, UK.
³¹ Department of Population Health Sciences, University of Leicester, Leicester, UK.
³² Department of Psychiatry and Behavioral Sciences, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA, USA.
³³ Centre for Brain and Cognitive Development, Department of Psychological Sciences, Birkbeck University of London, London, UK. a.ronald@surrey.ac.uk.
³⁴ School of Psychology, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, UK. a.ronald@surrey.ac.uk.

^# Contributed equally.

PMID: 40335706
DOI: 10.1038/s41562-025-02145-1

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.

Abstract

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