Epigenetic Profiling of Social Communication Trajectories and Co-occurring Mental Health Problems: A Prospective, Methylome-wide Association Study

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: N-birth=804, N-age7=877) and trajectories of social communication deficits (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 age 7. 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 late childhood to late 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. This dataset contains summary statistics for the methylome-wide association study using DNAm data collected from individuals at birth. Upload of this dataset was completed by The EWAS Catalog team. The data can be queried along with hundreds of other EWAS at ewascatalog.org. To upload your EWAS summary statistics and have a zenodo DOI generated for you go to ewascatalog.org/upload既往研究表明，遗传与环境因素在自闭症相关特质的发生发展中均发挥重要作用，但目前学界对这些关联背后的潜在生物学机制仍知之甚少。本研究利用雅芳父母与儿童纵向研究（Avon Longitudinal Study of Parents and Children, ALSPAC）的队列数据，考察了DNA甲基化（DNA methylation, DNAm：出生样本量N=804，7岁样本量N=877）与8至17岁社交沟通缺陷轨迹之间的前瞻性关联。全基因组范围内3个基因位点的甲基组变异（错误发现率（false discovery rate）=0.048）可有效区分社交沟通缺陷轨迹较高（n=80）与较低（n=724）的儿童群体。该差异甲基化特征仅存在于新生儿时期，在7岁年龄点未观察到类似现象。在校正共发心理健康问题（包括多动/注意力缺陷、品行问题）后，DNA甲基化水平与轨迹归属之间的关联依然保持稳健。本研究在出生时识别出的3个基因位点未在Generation R研究中得到重复验证。据我们所知，ALSPAC是目前唯一一项具备足够前瞻性的队列研究，可用于考察儿童晚期至青少年晚期社交沟通缺陷的纵向轨迹与DNA甲基化之间的关联。尽管本研究结果或可指向区分高低社交沟通缺陷轨迹的潜在新位点，但该结论仍属于初步探索结果，需待进一步重复验证后方可确认其可靠性。本数据集包含基于出生个体采集的DNA甲基化数据开展的全甲基组关联研究的汇总统计量。本数据集由EWAS Catalog团队完成上传。研究者可在ewascatalog.org平台查询该数据，同时可检索数百项其他表观全基因组关联研究（Epigenome-Wide Association Study, EWAS）。若需上传您的EWAS汇总统计量并获取Zenodo数字对象标识符（Digital Object Identifier, DOI），请访问ewascatalog.org/upload。