The Biological Embedding of Early Life Socioeconomic and Family Adversity in Children’s Genome-wide DNA Methylation

Early life social experiences are believed to confer persistent effects on individual’s biology and subsequent functioning and health. Using a diverse, longitudinal community sample of 178 children, we show that three different types of early life social experience: family income, parental education, and family psychosocial adversity, each predict DNA methylation within buccal epithelial cells. Each predictor was significantly associated with DNA methylation within a unique set of genomic CpG sites, with income showing the greatest number of associations. Findings were independently verified using pyrosequencing. Our results provide evidence for longitudinal associations between early life social environment and variation in DNA methylation during childhood, after adjusting for genetic ancestry and self-reported ethnic minority status. Gene ontology analyses of top, differentially methylated CpG sites point to genes serving immune and developmental regulation functions, suggesting potential pathways for the biological embedding of early life stress and its association with later development and health. This cohort consist of genomic DNA extracted from 178 buccal swabs, bisulphite converted and hybridized to the Illumina Infinium HumanMethylation450 Beadchip for genome wide DNA methylation profiling.早期社会经历被认为会对个体的生物学特征、后续社会功能与健康状况产生持久影响。 本研究采用包含178名儿童的多样化纵向社区样本，证实三类早期社会经历——家庭收入、父母受教育程度与家庭社会心理逆境——均可预测颊上皮细胞内的DNA甲基化（DNA methylation）水平。每一类预测因素均与一组独特的基因组CpG位点的DNA甲基化水平存在显著关联，其中家庭收入的关联数目最多。 本研究通过焦磷酸测序（pyrosequencing）对研究结果进行了独立验证。 在控制遗传血统与自我报告的少数族裔身份变量后，本研究结果证实早期社会环境与儿童时期DNA甲基化变异之间存在纵向关联。 对显著差异甲基化CpG位点的基因本体论（Gene ontology）分析显示，相关基因多参与免疫与发育调控功能，这提示了早期应激的生物学嵌入及其与后续发育和健康关联的潜在通路。 本队列的基因组DNA提取自178份颊拭子样本，经亚硫酸氢盐转化后，与Illumina Infinium HumanMethylation450 Beadchip芯片进行杂交，以开展全基因组DNA甲基化谱分析。