Maternal anxiety and depression in pregnancy and DNA methylation of the NR3C1 glucocorticoid receptor gene

Aim: To quantify associations of anxiety and depression during pregnancy with differential cord blood DNA methylation of the glucorticoid receptor ( NR3C1). Materials & methods: Pregnancy anxiety, trait anxiety and depressive symptoms were collected using the Pregnancy Related Anxiety Scale, State-Trait Anxiety Index and Edinburgh Postnatal Depression Scale, respectively. NR3C1 methylation was determined at four methylation sites. Results: DNA methylation of CpG 1 in the NR3C1 CpG island shore was higher in infants born to women with high pregnancy anxiety (β 2.54, 95% CI: 0.49–4.58) and trait anxiety (β 1.68, 95% CI: 0.14–3.22). No significant association was found between depressive symptoms and NR3C1 methylation. Conclusion: We found that maternal anxiety was associated with increased NR3C1 CpG island shore methylation.

Differential Methylation Signatures in Severely Calcified Carotid Plaques by Genome-Wide Comprehensive Analysis

Background: The precise cellular behaviors of calcification, including its molecular and genetic activities, have not yet been fully established for carotid plaques. Objective: We sought specific genes with tissue-specific differential methylation associated with carotid calcification status. Methods: We classified eight plaques from carotid endarterectomy patients as high- or low-calcified based on their Agatston calcium scores. We analyzed differential DNA methylation and performed bioinformatics data mining. Results: A high correlation of average methylation levels (b-values) in promoter regions between high- and low-calcified plaque groups was observed. A principal component analysis of DNA methylation values in promoters of specimens revealed two independent clusters for high- and low-calcified plaques. Volcano plots for methylation differences in promoter regions showed that significantly hypomethylated probes were more frequently found for high-calcified plaques than more methylated probes. Differential hypomethylation of receptor activity-modifying protein 1 (RAMP1) in high-calcified plaques was commonly extracted in both the promoter region and the cytosine-phosphate-guanine (CpG) island shore region, where differential methylation had been reported to be more tissue-specific. Kyoto Encyclopedia of Genes and Genomes pathway analysis annotated a pathway associated with vascular smooth muscle contraction in the differentially methylated genes of the promoter and CpG island shore regions in high-calcified plaques. Conclusion: Among the extracted differentially methylated genes, hypomethylated genes were more dominant than more methylated genes. The augmentation of RAMP1 by hypomethylation may contribute to the enhancement of antiatherosclerotic effects and hence stability in high-calcified plaques. These results contribute to our understanding of the genetic signatures associated with calcification status and cellular activity in carotid plaques.

GeneDMRs: an R package for Gene-based Differentially Methylated Regions analysis

DNA methylation in gene or promoter or gene body could restrict/promote the gene transcription. Moreover, methylation in the gene regions along with CpG island regions could modulate the transcription to undetectable gene expression levels. Therefore, it is necessary to investigate the methylation levels within the gene, gene body, CpG island regions and their overlapped regions and then identify the gene-based differentially methylated regions (GeneDMRs). Here, R package GeneDMRs aims to facilitate computing gene based methylation rate using next generation sequencing (NGS)-based methylome data. The user-friendly R package GeneDMRs is presented to analyze the methylation levels in each gene/promoter/exon/intron/CpG island/CpG island shore or each overlapped region (e.g., gene-CpG island/promoter-CpG island/exon-CpG island/intron-CpG island/gene-CpG island shore/promoter-CpG island shore/exon-CpG island shore/intron-CpG island shore). Here, we used the public reduced representation bisulfite sequencing (RRBS) data of mouse (GSE62392) for evaluating software and found novel biologically significant results to supplement the previous research. The R package GeneDMRs can facilitate computing gene based methylation rate to interpret complex interplay between methylation levels and gene expression differences or similarities across physiological conditions or disease states.