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 age 7. 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展中均发挥重要作用，但目前对这些关联背后的潜在生物学机制仍知之甚少。本研究借助雅芳父母与儿童纵向研究（Avon Longitudinal Study of Parents and Children, ALSPAC）的数据，探讨了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岁社交沟通缺陷发展轨迹之间的前瞻性关联。全基因组范围内的3个基因位点存在甲基组变异（错误发现率=0.048），可区分社交沟通缺陷轨迹高分组（n=80）与低分组（n=724）的儿童。该甲基化差异仅存在于新生儿期，在7岁时未观察到此现象。在校正共现的心理健康问题（即多动/注意力不集中、品行问题）后，DNA甲基化与轨迹归属的关联仍保持稳健。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。但据我们所知，雅芳父母与儿童纵向研究是目前唯一一项足够前瞻的研究，可探讨DNA甲基化与儿童晚期至青少年晚期社交沟通缺陷纵向轨迹之间的关联。尽管本研究结果可能指向可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，需待后续研究重复验证后方可确认。本数据集包含基于7岁个体DNA甲基化数据开展的表观基因组全关联研究（epigenome-wide association study, EWAS）的汇总统计量。本数据集由EWAS目录团队上传。用户可在ewascatalog.org平台查询该数据及数百项其他EWAS研究数据。若需上传您的EWAS汇总统计量并生成Zenodo数字对象标识符（Zenodo DOI），请访问ewascatalog.org/upload