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

IF 21.4 1区心理学 Q1 MULTIDISCIPLINARY SCIENCES

Nature Human Behaviour Pub Date : 2025-05-07 DOI:10.1038/s41562-025-02145-1

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

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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.

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7万多名欧洲血统婴儿开始行走年龄的全基因组关联荟萃分析

开始行走的年龄是临床和公共卫生筛查中使用的一个重要的儿童早期里程碑。在这项全基因组关联研究荟萃分析中（N = 70,560名欧洲血统婴儿），我们确定了11个独立的全基因组显著位点。snp遗传率为24.13%(95%置信区间为21.86 ~ 26.40)，约11900个变异约占遗传率的90%，具有较高的多基因性。其中一个基因座位于基因RBL2中，与大脑中的表达数量性状位点（eQTL）共定位。开始走路的年龄（以月为单位）与多动症和体重指数呈负相关，与婴儿和成人大脑的脑旋转呈正相关。多基因评分显示样本外预测为3-5.6%，这在很大程度上是由于兄弟姐妹对分析的直接影响，并且与参与运动控制的新生儿大脑结构的体积单独相关。这项研究为神经发育的关键行为标记提供了生物学上的见解。

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来源期刊

Nature Human Behaviour Psychology-Social Psychology

CiteScore

36.80

自引率

1.00%

发文量

227

期刊介绍： Nature Human Behaviour is a journal that focuses on publishing research of outstanding significance into any aspect of human behavior.The research can cover various areas such as psychological, biological, and social bases of human behavior.It also includes the study of origins, development, and disorders related to human behavior.The primary aim of the journal is to increase the visibility of research in the field and enhance its societal reach and impact.