BACKGROUND Perinatal depressive symptoms have been linked to adverse maternal and infant health outcomes. The etiology associated with perinatal depressive psychopathology is poorly understood, but accumulating evidence suggests that understanding inter-individual differences in DNA methylation (DNAm) patterning may provide insight regarding the genomic regions salient to the risk liability of perinatal depressive psychopathology. RESULTS Genome-wide DNAm was measured in maternal peripheral blood using the Infinium MethylationEPIC microarray. Ninety-two participants (46% African-American) had DNAm samples that passed all quality control metrics, and all participants were within 7 months of delivery. Linear models were constructed to identify differentially methylated sites and regions, and permutation testing was utilized to assess significance. Differentially methylated regions (DMRs) were defined as genomic regions of consistent DNAm change with at least two probes within 1 kb of each other. Maternal age, current smoking status, estimated cell-type proportions, ancestry-relevant principal components, days since delivery, and chip position served as covariates to adjust for technical and biological factors. Current postpartum depressive symptoms were measured using the Edinburgh Postnatal Depression Scale. Ninety-eight DMRs were significant (false discovery rate < 5%) and overlapped 92 genes. Three of the regions overlap loci from the latest Psychiatric Genomics Consortium meta-analysis of depression. CONCLUSIONS Many of the genes identified in this analysis corroborate previous allelic, transcriptomic, and DNAm association results related to depressive phenotypes. Future work should integrate data from multi-omic platforms to understand the functional relevance of these DMRs and refine DNAm association results by limiting phenotypic heterogeneity and clarifying if DNAm differences relate to the timing of onset, severity, duration of perinatal mental health outcomes of the current pregnancy or to previous history of depressive psychopathology.

中文翻译：

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与产后抑郁症状相关的DNA甲基化与抑郁症的全基因组关联荟萃分析的发现重叠。

背景技术围产期抑郁症状已与不良的母婴健康结局相关。与围产期抑郁症心理病理学相关的病因学知之甚少，但越来越多的证据表明，了解个体间DNA甲基化（DNAm）模式的差异可能会提供有关围产期抑郁症心理病理风险显着的基因组区域的见解。结果使用Infinium MethylationEPIC微阵列在孕妇外周血中测量了全基因组DNAm。92名参与者（占46％的非裔美国人）的DNAm样本通过了所有质量控制指标，所有参与者均在分娩后7个月内。构建线性模型以识别差异甲基化位点和区域，并使用置换测试评估重要性。差异甲基化区域（DMR）定义为DNAm变化一致的基因组区域，其中至少两个探针彼此相距1 kb。产妇年龄，当前吸烟状况，估计的细胞类型比例，与血统有关的主要成分，分娩后的天数和芯片的位置是根据技术和生物学因素进行调整的协变量。使用爱丁堡产后抑郁量表测量当前的产后抑郁症状。98个DMR显着（错误发现率<5％）并且重叠了92个基因。最新的精神病基因组学联盟对抑郁症的荟萃分析显示，其中三个区域重叠了基因座。结论在该分析中鉴定的许多基因证实了先前与抑郁表型相关的等位基因，转录组和DNAm关联结果。