Language delay is extremely common in children with autism spectrum disorder (ASD), yet it is unclear whether measurable variation in early language is associated with genetic liability for ASD. Assessment of language development in unaffected siblings of children with ASD can inform whether decreased early language ability aggregates with inherited risk for ASD and serves as an ASD endophenotype. We implemented two approaches: (1) a meta-analysis of studies comparing language delay, a categorical indicator of language function, and language scores, a continuous metric, in unaffected toddlers at high and low familial risk for ASD, and (2) a parallel analysis of 350 unaffected 24-month-olds in the Infant Brain Imaging Study (IBIS), a prospective study of infants at high and low familial risk for ASD. An advantage of the former was its detection of group differences from pooled data across unique samples; an advantage of the latter was its sensitivity in quantifying early manifestations of language delay while accounting for covariates within a single large sample. Meta-analysis showed that high-risk siblings without ASD (HR-noASD) were three to four times more likely to exhibit language delay versus low-risk siblings without ASD (LR-noASD) and had lower mean receptive and expressive language scores. Analyses of IBIS data corroborated that language delay, specifically receptive language delay, was more frequent in the HR-noASD (n = 235) versus LR-noASD group (n = 115). IBIS language scores were continuously and unimodally distributed, with a pathological shift towards decreased language function in HR-noASD siblings. The elevated inherited risk for ASD was associated with lower receptive and expressive language scores when controlling for sociodemographic factors. For receptive but not expressive language, the effect of risk group remained significant even when controlling for nonverbal cognition. Greater frequency of language delay and a lower distribution of language scores in high-risk, unaffected toddler-aged siblings support decreased early language ability as an endophenotype for ASD, with a more pronounced effect for receptive versus expressive language. Further characterization of language development is warranted to refine genetic investigations of ASD and to elucidate factors influencing the progression of core autistic traits and related symptoms.

中文翻译：

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患有自闭症谱系障碍的儿童的幼儿兄弟姐妹中的语言发育迟缓会集中出现。

语言发育迟缓在患有自闭症谱系障碍 (ASD) 的儿童中极为常见，但尚不清楚早期语言的可测量变异是否与 ASD 的遗传倾向相关。对患有自闭症谱系障碍 (ASD) 儿童的未受影响兄弟姐妹的语言发展进行评估，可以了解早期语言能力下降是否与自闭症谱系障碍 (ASD) 遗传风险相结合，并作为自闭症谱系障碍 (ASD) 内表型。我们实施了两种方法：(1) 对具有高和低自闭症谱系障碍家族风险的未受影响幼儿的语言延迟（语言功能的校准指标）和语言分数（连续指标）进行比较研究的荟萃分析，以及 (2)婴儿脑成像研究 (IBIS) 对 350 名未受影响的 24 个月大的婴儿进行了平行分析，该研究是一项针对 ASD 家族高风险和低风险婴儿的前瞻性研究。前者的一个优点是它可以从独特样本的汇总数据中检测群体差异。后者的优点是其在量化语言延迟的早期表现方面的敏感性，同时考虑单个大样本内的协变量。荟萃分析显示，无 ASD 的高风险兄弟姐妹 (HR-noASD) 表现出语言延迟的可能性是无 ASD 的低风险兄弟姐妹 (LR-noASD) 的三到四倍，并且平均接受性和表达性语言得分较低。IBIS 数据分析证实，与 LR-noASD 组 (n = 115) 相比，HR-noASD (n = 235) 组中语言延迟，特别是接受性语言延迟更为常见。IBIS 语言评分呈连续单峰分布，HR-noASD 兄弟姐妹的语言功能出现病理性转变。在控制社会人口统计学因素时，自闭症谱系障碍遗传风险的升高与接受性和表达性语言得分较低有关。对于接受性而非表达性语言，即使在控制非语言认知的情况下，风险群体的影响仍然显着。在高风险、未受影响的幼儿兄弟姐妹中，语言延迟的发生频率较高，且语言分数分布较低，这支持早期语言能力下降，这是自闭症谱系障碍的一种内表型，对接受性语言的影响比表达性语言的影响更明显。需要进一步表征语言发展，以完善自闭症谱系障碍的遗传研究，并阐明影响自闭症核心特征和相关症状进展的因素。