Genome-wide association meta-analysis of age at onset of walking in over 70,000 infants of European ancestry.
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Springer Nature
https://doi.org/10.1038/s41562-025-02145-1
https://doi.org/10.1038/s41562-025-02145-1
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Funder: South-Eastern Norway Regional Health Authority (#2019097,#2022083)
Funder: South-Eastern Norway Regional Health Authority (#2021045)
Funder: HC is an academic clinical lecturer in Clinical Genetics at Kings College London and her research is supported by the NIHR.
Funder: UKRI (10063472)
Funder: KG Jebsen Stiftelsen
Funder: European Research Council Consolidator Grant (771057) NWO Vici scheme (VI.C.211.054 504)
Funder: KNAW Academy Professor Award (PAH/6635)
Funder: South-Eastern Norway Regional Health Authority (#2020022; #2019097)
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.
Funder: South-Eastern Norway Regional Health Authority (#2021045)
Funder: HC is an academic clinical lecturer in Clinical Genetics at Kings College London and her research is supported by the NIHR.
Funder: UKRI (10063472)
Funder: KG Jebsen Stiftelsen
Funder: European Research Council Consolidator Grant (771057) NWO Vici scheme (VI.C.211.054 504)
Funder: KNAW Academy Professor Award (PAH/6635)
Funder: South-Eastern Norway Regional Health Authority (#2020022; #2019097)
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.