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对70000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。

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

作者信息

Gui Anna, Hollowell Anja, Wigdor Emilie M, Morgan Morgan J, Hannigan Laurie J, Corfield Elizabeth C, Odintsova Veronika, Hottenga Jouke-Jan, Wong Andrew, Pool René, Cullen Harriet, Wilson Siân, Warrier Varun, Eilertsen Espen M, Andreassen Ole A, Middeldorp Christel M, St Pourcain Beate, Bartels Meike, Boomsma Dorret I, Hartman Catharina A, Robinson Elise B, Arichi Tomoki, Edwards Anthony D, Johnson Mark H, Dudbridge Frank, Sanders Stephan J, Havdahl Alexandra, Ronald Angelica

机构信息

Department of Psychology, University of Essex, Wivenhoe Park, Colchester, UK.

Centre for Brain and Cognitive Development, Department of Psychological Sciences, Birkbeck University of London, London, UK.

出版信息

Nat Hum Behav. 2025 May 7. 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.

摘要

开始走路的年龄是幼儿期的一个重要里程碑,在临床和公共卫生筛查中都会用到。在这项针对开始走路年龄的全基因组关联研究荟萃分析中(N = 70560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。基于单核苷酸多态性的遗传力为24.13%(95%置信区间 = 21.86 - 26.40),约11900个变异占其中的90%左右,表明具有高度多基因性。这些位点之一位于基因RBL2中,与大脑中的一个表达数量性状位点(eQTL)共定位。开始走路的年龄(以月为单位)与注意力缺陷多动障碍和体重指数呈负遗传相关,与婴儿和成人大脑的脑回形成呈正遗传相关。多基因评分显示样本外预测率为3 - 5.6%,在同胞对分析中证实主要是由于直接效应,并且分别与参与运动控制的新生儿脑结构体积相关。这项研究为神经发育的一个关键行为标志物提供了生物学见解。

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