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

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. HartmanElise B. Robinson, Tomoki Arichi, Anthony D. Edwards, Mark H. Johnson, Frank Dudbridge, Stephan J. Sanders, Alexandra Havdahl, Angelica Ronald^*

^*Corresponding author for this work

Research output: Contribution to journal › Article (Academic Journal) › peer-review

2 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1470-1487
Number of pages	18
Journal	Nature Human Behaviour
Volume	9
Issue number	7
Early online date	7 May 2025
DOIs	https://doi.org/10.1038/s41562-025-02145-1
Publication status	Published - 1 Jul 2025

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© The Author(s) 2025.

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Gui, A., Hollowell, A., Wigdor, E. M., Morgan, M. J., Hannigan, L. J., Corfield, E. C., Odintsova, V., Hottenga, J. J., Wong, A., Pool, R., Cullen, H., Wilson, S., Warrier, V., Eilertsen, E. M., Andreassen, O. A., Middeldorp, C. M., St Pourcain, B., Bartels, M., Boomsma, D. I., ... Ronald, A. (2025). Genome-wide association meta-analysis of age at onset of walking in over 70,000 infants of European ancestry. Nature Human Behaviour, 9(7), 1470-1487. https://doi.org/10.1038/s41562-025-02145-1

@article{88a41eea2e4e430e95fb3b5738398d82,

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

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 \textasciitilde{}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.",

author = "Anna Gui and Anja Hollowell and Wigdor, \{Emilie M.\} and Morgan, \{Morgan J.\} and Hannigan, \{Laurie J.\} and Corfield, \{Elizabeth C.\} and Veronika Odintsova and Hottenga, \{Jouke Jan\} and Andrew Wong and Ren{\'e} Pool and Harriet Cullen and Si{\^a}n Wilson and Varun Warrier and Eilertsen, \{Espen M.\} and Andreassen, \{Ole A.\} and Middeldorp, \{Christel M.\} and \{St Pourcain\}, Beate and Meike Bartels and Boomsma, \{Dorret I.\} and Hartman, \{Catharina A.\} and Robinson, \{Elise B.\} and Tomoki Arichi and Edwards, \{Anthony D.\} and Johnson, \{Mark H.\} and Frank Dudbridge and Sanders, \{Stephan J.\} and Alexandra Havdahl and Angelica Ronald",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2025.",

year = "2025",

month = jul,

day = "1",

doi = "10.1038/s41562-025-02145-1",

language = "English",

volume = "9",

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journal = "Nature Human Behaviour",

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Gui, A, Hollowell, A, Wigdor, EM, Morgan, MJ, Hannigan, LJ, Corfield, EC, Odintsova, V, Hottenga, JJ, Wong, A, Pool, R, Cullen, H, Wilson, S, Warrier, V, Eilertsen, EM, Andreassen, OA, Middeldorp, CM, St Pourcain, B, Bartels, M, Boomsma, DI, Hartman, CA, Robinson, EB, Arichi, T, Edwards, AD, Johnson, MH, Dudbridge, F, Sanders, SJ, Havdahl, A & Ronald, A 2025, 'Genome-wide association meta-analysis of age at onset of walking in over 70,000 infants of European ancestry', Nature Human Behaviour, vol. 9, no. 7, pp. 1470-1487. https://doi.org/10.1038/s41562-025-02145-1

TY - JOUR

T1 - Genome-wide association meta-analysis of age at onset of walking in over 70,000 infants of European ancestry

AU - Gui, Anna

AU - Hollowell, Anja

AU - Wigdor, Emilie M.

AU - Morgan, Morgan J.

AU - Hannigan, Laurie J.

AU - Corfield, Elizabeth C.

AU - Odintsova, Veronika

AU - Hottenga, Jouke Jan

AU - Wong, Andrew

AU - Pool, René

AU - Cullen, Harriet

AU - Wilson, Siân

AU - Warrier, Varun

AU - Eilertsen, Espen M.

AU - Andreassen, Ole A.

AU - Middeldorp, Christel M.

AU - St Pourcain, Beate

AU - Bartels, Meike

AU - Boomsma, Dorret I.

AU - Hartman, Catharina A.

AU - Robinson, Elise B.

AU - Arichi, Tomoki

AU - Edwards, Anthony D.

AU - Johnson, Mark H.

AU - Dudbridge, Frank

AU - Sanders, Stephan J.

AU - Havdahl, Alexandra

AU - Ronald, Angelica

PY - 2025/7/1

Y1 - 2025/7/1

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/105004575501

U2 - 10.1038/s41562-025-02145-1

DO - 10.1038/s41562-025-02145-1

M3 - Article (Academic Journal)

C2 - 40335706

AN - SCOPUS:105004575501

SN - 2397-3374

VL - 9

SP - 1470

EP - 1487

JO - Nature Human Behaviour

JF - Nature Human Behaviour

IS - 7

ER -

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

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