While previous studies suggest that both genetic and environmental factors play an important role in the development of autism-related traits, little is known about potential biological mechanisms underlying these associations. Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC), we examined prospective associations between DNA methylation (DNAm: nbirth = 804, nage 7 = 877) and trajectories of social communication deficits at age 8–17 years. Methylomic variation at three loci across the genome (false discovery rate = 0.048) differentiated children following high (n = 80) versus low (n = 724) trajectories of social communication deficits. This differential DNAm was specific to the neonatal period and not observed at 7 years of age. Associations between DNAm and trajectory membership remained robust after controlling for co-occurring mental health problems (i.e., hyperactivity/inattention, conduct problems). The three loci identified at birth were not replicated in the Generation R Study. However, to the best of our knowledge, ALSPAC is the only study to date that is prospective enough to examine DNAm in relation to longitudinal trajectories of social communication deficits from childhood to adolescence. Although the present findings might point to potentially novel sites that differentiate between a high versus low trajectory of social communication deficits, the results should be considered tentative until further replicated.

虽然之前的研究表明遗传和环境因素在自闭症相关特征的发展中起着重要作用，但人们对这些关联背后的潜在生物学机制知之甚少。使用来自雅芳父母和儿童纵向研究 (ALSPAC) 的数据，我们检查了 DNA 甲基化（DNAm：n出生= 804，n年龄= 877）与 8-17 岁社会沟通缺陷轨迹之间的前瞻性关联。基因组中三个基因座的甲基化变异（错误发现率 = 0.048）区分了高（n = 80）与低（n= 724) 社会沟通缺陷的轨迹。这种差异 DNAm 是新生儿期特有的，在 7 岁时未观察到。在控制了同时发生的心理健康问题（即多动/注意力不集中、行为问题）后，DNAm 和轨迹成员之间的关联仍然稳健。出生时确定的三个位点未在 Generation R 研究中重复。然而，据我们所知，ALSPAC 是迄今为止唯一一项前瞻性足以检验 DNAm 与从童年到青春期社会沟通缺陷的纵向轨迹相关的研究。尽管目前的研究结果可能指向潜在的新站点，这些站点可以区分社交沟通缺陷的高轨迹和低轨迹，但在进一步复制之前，应将结果视为暂定的。