Dataset Information

Genome-Wide DNA Methylation Patterns in Children Exposed to Nonpharmacologically Treated Prenatal Depressive Symptoms: Results From 2 Independent Cohorts.

ABSTRACT: Background:Maternal depressive symptoms are a common phenomenon during pregnancy and are related to negative outcomes for child development and health. Modifications in child DNA methylation are discussed as an underlying mechanism for the association between prenatal depressive symptoms and alterations in child outcomes. However, formerly reported genome-wide associations have yet to be replicated. Methods:In an epigenome-wide association study (EWAS), alterations of DNA methylation related to maternal prenatal depressive symptoms were investigated in buccal cell samples from 174 children (n?=?52 exposed to prenatal depressive symptoms; 6-9?years old) of the German longitudinal study FRAMES-FRANCES. Whole blood samples from the independent, age-comparable ARIES subsample of the ARIES/ALSPAC study (n?=?641; n?=?159 exposed to prenatal depressive symptoms; 7-8?years old) were examined as a confirmation sample. Depressive symptoms were assessed with the Edinburgh Postnatal Depression Scale. DNA methylation was analyzed with the Infinium Human Methylation 450k BeadChip. Modifications in single CpGs, regions, and biological pathways were investigated. Results were adjusted for age and birth outcomes as well as postnatal and current maternal depressive symptoms. Analyses were performed for the whole sample as well as separated for sex. Results:The EWAS yielded no differentially methylated CpG or region as well as no accordance between samples withstanding correction for multiple testing. In pathway analyses, no overlapping functional domain was found to be enriched for either sample. A comparison of current and former findings suggests some overlapping methylation modifications from infancy to childhood. Results suggest that there might be sex-specific differential methylation, which should be further investigated in additional studies. Conclusions:The current, mainly nonsignificant, results challenge the assumption of consistent modifications of DNA methylation in children exposed to prenatal depressive symptoms. Despite the relatively small sample size used in this study, this lack of significant results may reflect diverse issues of environmental epigenetic studies, which need to be addressed in future research.

SUBMITTER: Stonawski V

PROVIDER: S-EPMC7298426 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Genome-Wide DNA Methylation Patterns in Children Exposed to Nonpharmacologically Treated Prenatal Depressive Symptoms: Results From 2 Independent Cohorts.

Stonawski Valeska V Roetner Jakob J Goecke Tamme W TW Fasching Peter A PA Beckmann Matthias W MW Kornhuber Johannes J Kratz Oliver O Moll Gunther H GH Eichler Anna A Heinrich Hartmut H Frey Stefan S

Epigenetics insights 20200616

<h4>Background</h4>Maternal depressive symptoms are a common phenomenon during pregnancy and are related to negative outcomes for child development and health. Modifications in child DNA methylation are discussed as an underlying mechanism for the association between prenatal depressive symptoms and alterations in child outcomes. However, formerly reported genome-wide associations have yet to be replicated.<h4>Methods</h4>In an epigenome-wide association study (EWAS), alterations of DNA methylat ...[more]

PMID: 32596638

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Project description:BackgroundPrenatal symptoms of depression (PND) and anxiety affect up to every third pregnancy. Children of mothers with mental health problems are at higher risk of developmental problems, possibly through epigenetic mechanisms together with other factors such as genetic and environmental. We investigated DNA methylation in cord blood in relation to PND, taking into consideration a history of depression, co-morbidity with anxiety and selective serotonin reuptake inhibitors (SSRI) use, and stratified by sex of the child. Mothers (N = 373) prospectively filled out web-based questionnaires regarding mood symptoms and SSRI use throughout pregnancy. Cord blood was collected at birth and DNA methylation was measured using Illumina MethylationEPIC array at 850 000 CpG sites throughout the genome. Differentially methylated regions were identified using Kruskal-Wallis test, and Benjamini-Hochberg adjusted p-values < 0.05 were considered significant.ResultsNo differential DNA methylation was associated with PND alone; however, differential DNA methylation was observed in children exposed to comorbid PND with anxiety symptoms compared with healthy controls in ABCF1 (log twofold change - 0.2), but not after stratification by sex of the child. DNA methylation in children exposed to PND without SSRI treatment and healthy controls both differed in comparison with SSRI exposed children at several sites and regions, among which hypomethylation was observed in CpGs in the promoter region of CRBN (log2 fold change - 0.57), involved in brain development, and hypermethylation in MDFIC (log2 fold change 0.45), associated with the glucocorticoid stress response.ConclusionAlthough it is not possible to assess if these methylation differences are due to SSRI treatment itself or to more severe depression, our findings add on to existing knowledge that there might be different biological consequences for the child depending on whether maternal PND was treated with SSRIs or not.

Project description:Older adults are more susceptible to higher inflammatory levels and depression. Moreover, diet may influence inflammation as well as depression but no previous study examined whether inflammatory dietary patterns are related to depression in an older population. To investigate the longitudinal association between inflammatory dietary patterns (using reduced rank regression (RRR)) and depressive symptoms in a population sample of Italian older adults.We included 827 participants (aged?65years) at baseline in 1998. Follow-up measurements were collected after 3, 6 and 9years. We used RRR to identify inflammatory dietary patterns at baseline. The Centre for Epidemiologic Studies Depression (CES-D) scale was used to assess depressive symptoms by using continuous scores and depression by using a cut-off point (CES-D?20).We identified two inflammatory dietary patterns using different sets of response variables. Dietary pattern I was related to inflammatory markers C-reactive protein (CRP), interleukin (IL)-6, tumor necrosis factor ? and was characterized by high intakes of refined grains, sweet snacks, pasta and rice. After full adjustment for confounders, no longitudinal association was found when comparing extreme quartiles of this dietary pattern and depressive symptoms (Q1vs Q4, model 4: B=0.04, 95% CI: -0.06, 0.13) or depression (Q1vs Q4, model 4: OR=0.90, 95% CI: 0.55, 1.45). Dietary pattern II was related to inflammatory markers CRP, IL-18, IL-1?, IL-1 receptor antagonist and was characterized by high intakes of pasta, sugar-sweetened beverages, processed meat and chocolate and sweets. When comparing extreme quartiles, this dietary pattern was not longitudinally associated with depressive symptoms (Q1vs Q4, model 4: B=-0.04, 95% CI: -0.13, 0.05) but an inverse association was found for depression (Q1vs Q4, model 4: OR=0.56, 95% CI: 0.40, 0.94).Our study does not support the hypothesis that dietary patterns linked to inflammatory markers are associated with higher depressive symptoms and higher depression incidence. However, dietary intake in our population of older adults was quite homogeneous which makes it difficult to show clear associations.

Project description:BackgroundEpigenome-wide association studies (EWAS) have identified CpG sites associated with HIV infection in blood cells in bulk, which offer limited knowledge of cell-type specific methylation patterns associated with HIV infection. In this study, we aim to identify differentially methylated CpG sites for HIV infection in immune cell types: CD4+ T-cells, CD8+ T-cells, B cells, Natural Killer (NK) cells, and monocytes.MethodsApplying a computational deconvolution method, we performed a cell-type based EWAS for HIV infection in three independent cohorts (Ntotal = 1,382). DNA methylation in blood or in peripheral blood mononuclear cells (PBMCs) was profiled by an array-based method and then deconvoluted by Tensor Composition Analysis (TCA). The TCA-computed CpG methylation in each cell type was first benchmarked by bisulfite DNA methylation capture sequencing in a subset of the samples. Cell-type EWAS of HIV infection was performed in each cohort separately and a meta-EWAS was conducted followed by gene set enrichment analysis.ResultsThe meta-analysis unveiled a total of 2,021 cell-type unique significant CpG sites for five inferred cell types. Among these inferred cell-type unique CpG sites, the concordance rate in the three cohorts ranged from 96% to 100% in each cell type. Cell-type level meta-EWAS unveiled distinct patterns of HIV-associated differential CpG methylation, where 74% of CpG sites were unique to individual cell types (false discovery rate, FDR <0.05). CD4+ T-cells had the largest number of unique HIV-associated CpG sites (N = 1,624) compared to any other cell type. Genes harboring significant CpG sites are involved in immunity and HIV pathogenesis (e.g. CD4+ T-cells: NLRC5, CX3CR1, B cells: IFI44L, NK cells: IL12R, monocytes: IRF7), and in oncogenesis (e.g. CD4+ T-cells: BCL family, PRDM16, monocytes: PRDM16, PDCD1LG2). HIV-associated CpG sites were enriched among genes involved in HIV pathogenesis and oncogenesis that were enriched among interferon-α and -γ, TNF-α, inflammatory response, and apoptotic pathways.ConclusionOur findings uncovered computationally inferred cell-type specific modifications in the host epigenome for people with HIV that contribute to the growing body of evidence regarding HIV pathogenesis.

Dataset Information

Genome-Wide DNA Methylation Patterns in Children Exposed to Nonpharmacologically Treated Prenatal Depressive Symptoms: Results From 2 Independent Cohorts.

Publications

Genome-Wide DNA Methylation Patterns in Children Exposed to Nonpharmacologically Treated Prenatal Depressive Symptoms: Results From 2 Independent Cohorts.

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