BACKGROUND Impaired neuromotor development is often one of the earliest observations in children with autism spectrum disorder (ASD). We investigated whether a genetic predisposition to developmental disorders was associated with nonoptimal neuromotor development during infancy and examined the genetic correlation between nonoptimal neuromotor development and autistic traits in the general population. METHODS In a population-based cohort in The Netherlands (2002-2006), we calculated polygenic risk scores (PRSs) for ASD and attention-deficit/hyperactivity disorder (ADHD) using genome-wide association study summary statistics. In 1921 children with genetic data, parents rated autistic traits at 6 years of age. Among them, 1174 children (61.1%) underwent neuromotor examinations (tone, responses, senses, and other observations) during infancy (9-20 weeks of age). We used linear regressions to examine associations of PRSs with neuromotor scores and autistic traits. We performed a bivariate genome-based restricted maximum likelihood analysis to explore whether genetic susceptibility underlies the association between neuromotor development and autistic traits. RESULTS Higher PRSs for ASD were associated with less optimal overall infant neuromotor development, in particular low muscle tone. Higher PRSs for ADHD were associated with less optimal senses. PRSs for ASD and those for ADHD both were associated with autistic traits. The single nucleotide polymorphism-based heritability of overall motor development was 20% (SE = .21) and of autistic traits was 68% (SE = .26). The genetic correlation between overall motor development and autistic traits was .35 (SE = .21, p < .001). CONCLUSIONS We found that genetic liabilities for ASD and ADHD covary with neuromotor development during infancy. Shared genetic liability might partly explain the association between nonoptimal neuromotor development during infancy and autistic traits in childhood.

中文翻译：

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发育障碍、婴儿期神经运动功能和儿童自闭症特征的多基因风险评分

背景 神经运动发育受损通常是自闭症谱系障碍 (ASD) 儿童最早的观察结果之一。我们调查了发育障碍的遗传易感性是否与婴儿时期的非最佳神经运动发育有关，并检查了一般人群中非最佳神经运动发育与自闭症特征之间的遗传相关性。方法 在荷兰（2002-2006 年）的一个基于人群的队列中，我们使用全基因组关联研究汇总统计数据计算了 ASD 和注意力缺陷/多动障碍 (ADHD) 的多基因风险评分 (PRS)。在 1921 年有遗传数据的儿童中，父母在 6 岁时对自闭症特征进行了评级。其中，1174 名儿童（61.1%）接受了神经运动检查（语气、反应、感觉、和其他观察）在婴儿期（9-20 周大）。我们使用线性回归来检查 PRS 与神经运动评分和自闭症特征的关联。我们进行了基于双变量基因组的受限最大似然分析，以探索遗传易感性是否是神经运动发育和自闭症特征之间关联的基础。结果 ASD 较高的 PRS 与较不理想的整体婴儿神经运动发育相关，尤其是低肌张力。ADHD 较高的 PRS 与较不理想的感觉相关。ASD 和 ADHD 的 PRS 都与自闭症特征相关。整体运动发育的基于单核苷酸多态性的遗传率为 20% (SE = .21)，自闭症特征的遗传率为 68% (SE = .26)。整体运动发育与自闭症特征之间的遗传相关性为 . 35（SE = .21，p < .001）。结论 我们发现 ASD 和 ADHD 的遗传倾向与婴儿时期的神经运动发育有关。共同的遗传责任可能部分解释了婴儿期神经运动发育不佳与儿童期自闭症特征之间的关联。