scholarly journals DNA Methylation Associated with Postpartum Depressive Symptoms Overlaps Findings from a Genome-wide Association Meta-Analysis of Depression

2019 ◽  
Author(s):  
Dana M. Lapato ◽  
Roxann Roberson-Nay ◽  
Robert M. Kirkpatrick ◽  
Bradley T. Webb ◽  
Timothy P. York ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Depressive Symptoms ◽  
Health Outcomes ◽  
Meta Analysis ◽  
Previous History ◽  
Depression Scale ◽  
Postpartum Depressive Symptoms ◽  
Genome Wide ◽  
A Genome ◽  
Genomic Regions

AbstractBackgroundPerinatal 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.ResultsGenome-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 seven 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 1kb 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. Synaptic signaling, neural development, and platelet formation were the most represented biological processes in gene set analysis, and comparison to the 44 loci discovered in the latest Psychiatric Genomics Consortium meta-analysis of depression revealed 3 overlapping regions and significant enrichment (p<0.03).ConclusionsMany 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.

scholarly journals DNA methylation associated with postpartum depressive symptoms overlaps findings from a genome-wide association meta-analysis of depression

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Dana M. Lapato ◽  
Roxann Roberson-Nay ◽  
Robert M. Kirkpatrick ◽  
Bradley T. Webb ◽  
Timothy P. York ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Depressive Symptoms ◽  
Health Outcomes ◽  
Meta Analysis ◽  
Previous History ◽  
Depression Scale ◽  
Postpartum Depressive Symptoms ◽  
Genome Wide ◽  
A Genome ◽  
Genomic Regions

Abstract 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.

scholarly journals Genome-wide gene expression changes in postpartum depression point towards an altered immune landscape

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Divya Mehta ◽  
Karen Grewen ◽  
Brenda Pearson ◽  
Shivangi Wani ◽  
Leanne Wallace ◽  
...  
Keyword(s):  
Gene Expression ◽  
Depressive Symptoms ◽  
Postpartum Depression ◽  
Expression Profiles ◽  
Depression Scale ◽  
Well Being ◽  
Health Concern ◽  
Genome Wide ◽  
A Genome ◽  
Genome Wide Gene Expression

AbstractMaternal postpartum depression (PPD) is a significant public health concern due to the severe negative impact on maternal and child health and well-being. In this study, we aimed to identify genes associated with PPD. To do this, we investigated genome-wide gene expression profiles of pregnant women during their third trimester of pregnancy and tested the association of gene expression with perinatal depressive symptoms. A total of 137 women from a cohort from the University of North Carolina, USA were assessed. The main phenotypes analysed were Edinburgh Postnatal Depression Scale (EPDS) scores at 2 months postpartum and PPD (binary yes/no) based on an EPDS cutoff of 10. Illumina NextSeq500/550 transcriptomic sequencing from whole blood was analysed using the edgeR package. We identified 71 genes significantly associated with postpartum depression scores at 2 months, after correction for multiple testing at 5% FDR. These included several interesting candidates including TNFRSF17, previously reported to be significantly upregulated in women with PPD and MMP8, a matrix metalloproteinase gene, associated with depression in a genome-wide association study. Functional annotation of differentially expressed genes revealed an enrichment of immune response-related biological processes. Additional analysis of genes associated with changes in depressive symptoms from recruitment to 2 months postpartum identified 66 genes significant at an FDR of 5%. Of these genes, 33 genes were also associated with depressive symptoms at 2 months postpartum. Comparing the results with previous studies, we observed that 15.4% of genes associated with PPD in this study overlapped with 700 core maternal genes that showed significant gene expression changes across multiple brain regions (P = 7.9e-05) and 29–53% of the genes were also associated with estradiol changes in a pharmacological model of depression (P values range = 1.2e-4–2.1e-14). In conclusion, we identified novel genes and validated genes previously associated with oestrogen sensitivity in PPD. These results point towards the role of an altered immune transcriptomic landscape as a vulnerability factor for PPD.

scholarly journals Meta-Analysis of Genome-Wide Association Studies Identifies Novel Functional CpG-SNPs Associated with Bone Mineral Density at Lumbar Spine

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Chuan Qiu ◽  
Hui Shen ◽  
Xiaoying Fu ◽  
Chao Xu ◽  
Hongwen Deng
Keyword(s):  
Bone Mineral Density ◽  
Dna Methylation ◽  
Lumbar Spine ◽  
Bone Mineral ◽  
Meta Analysis ◽  
Mineral Density ◽  
Significance Level ◽  
Genome Wide ◽  
A Genome ◽  
Genome Wide Significance

Osteoporosis is a serious public health issue, which is mostly characterized by low bone mineral density (BMD). To search for additional genetic susceptibility loci underlying BMD variation, an effective strategy is to focus on testing of specific variants with high potential of functional effects. Single nucleotide polymorphisms (SNPs) that introduce or disrupt CpG dinucleotides (CpG-SNPs) may alter DNA methylation levels and thus represent strong candidate functional variants. Here, we performed a targeted GWAS for 63,627 potential functional CpG-SNPs that may affect DNA methylation in bone-related cells, in five independent cohorts (n=5905). By meta-analysis, 9 CpG-SNPs achieved a genome-wide significance level (p<7.86×10−7) for association with lumbar spine BMD and additional 15 CpG-SNPs showed suggestive significant (p<5.00×10−5) association, of which 2 novel SNPs rs7231498 (NFATC1) and rs7455028 (ESR1) also reached a genome-wide significance level in the joint analysis. Several identified CpG-SNPs were mapped to genes that have not been reported for association with BMD in previous GWAS, such as NEK3 and NFATC1 genes, highlighting the enhanced power of targeted association analysis for identification of novel associations that were missed by traditional GWAS. Interestingly, several genomic regions, such as NEK3 and LRP5 regions, contained multiple significant/suggestive CpG-SNPs for lumbar spine BMD, suggesting that multiple neighboring CpG-SNPs may synergistically mediate the DNA methylation level and gene expression pattern of target genes. Furthermore, functional annotation analyses suggested a strong regulatory potential of the identified BMD-associated CpG-SNPs and a significant enrichment in biological processes associated with protein localization and protein signal transduction. Our results provided novel insights into the genetic basis of BMD variation and highlighted the close connections between genetic and epigenetic mechanisms of complex disease.

GEJALA DEPRESI POSTPARTUM MEMPENGARUHI KEBERHASILAN ASI EKSKLUSIF : Sistematik Literatur Riview

2020 ◽  
pp. 27-34
Author(s):  
Nova Arami ◽  
Surahma Asti Mulasari ◽  
Ummu Hani EN
Keyword(s):  
Depressive Symptoms ◽  
Breast Milk ◽  
Postpartum Depression ◽  
Low Income ◽  
Critical Appraisal ◽  
Previous History ◽  
Synthesis Method ◽  
Depression Scale ◽  
Postpartum Depressive Symptoms ◽  
Postpartum Mothers

Air Susu Ibu (ASI) merupakan satu-satunya makanan yang sempurna dan terbaik bagi bayi karena mengandung unsur-unsur gizi yang dibutuhkan untuk pertumbuhan dan perkembangan bayi yang optimal. Namun ada beberapa penyebab ibu tidak memberikan ASI secara eksklusif seperti tidak mendapatkan dukungan dari suami/keluarga, penghasilan, usia, pendidikan yang menyebabkan terjadinya depresi postpartum sehingga menghambat proses laktasi. Tujuan penelitian untuk menyimpulkan dan memeriksa literature (examine literature) apakah gejala depresi pada ibu postpartum berhubungan dengan  keberhasilan pemberian ASI. Metode penelitian menggunakan studi appraisal dengan Critical Appraisal Joana Brigs Institute, dan metode sintesis menggunakan PEOS. Pencarian dibatasi pada studi yang diterbitkan dalam bahasa Inggris dan menyajikan data periode 2012-2019. Studi yang terindentifikasi ditinjau menggunakan PRISMA Flowchart. Studi dengan desain kuantitatif terkait gejala depresi postpartum mempengaruhi keberhasilan ASI eksklusif. Hasil penelitian adalah depresi postpartum diukur menggunakan EPDS (Edinburgh Postpartum Depression Scale) yang dilakukan pada ibu postpartum usia 2-6 minggu pascapersalinan. Gejala depresi dapat mempengaruhi keberhasilan pemberian ASI dan beberapa faktornya karena kurangnya dukungan emosional, pendidikan, pengetahuan, pendapatan yang rendah, dan terdapat riwayat depresi sebelumnya. Namun hal yang paling dominan terjadinya depresi postpartum yaitu kurangnya dukungan suami/keluarga. Kesimpulan penelitian ini adalah gejala depresi postpartum dapat mempengaruhi keberhasilan ASI eksklusif dikarenakan ada perubahan hormon dan mood yang terjadi pada ibu seperti tidak nafsu makan, gangguan tidur, cemas, sensitif sehingga dapat menggaggu kelancaran ASI. Breastmilk (ASI) is the only perfect and best food for babies because it contains nutritional elements for optimal baby growth and development. However, there are several reasons why mothers do not exclusively breastfeed, such as not getting support from their husbands/families, stage, education which causes postpartum depression which hinders the lactation process. This study aims to conclude and examine the literature (examining the literature) whether the symptoms of depression in postpartum mothers are associated with breastfeeding. The method of the study using appraisal study using Joana Brigs Institute Critical Appraisal, and synthesis method using PEOS. Base search on studies published in English and present data for the period 2012-2019. Identified studies were reviewed using PRISMA Flowchart. A quantitative design study of postpartum depressive symptoms affects exclusive breastfeeding. The results showed postpartum depression was measured using the EPDS (Edinburgh Postpartum Depression Scale) which was performed on postpartum mothers aged 2-6 weeks postpartum. Depressive symptoms can affect the situation of offering breast milk and several factors due to emotional support, education, low income, a previous history of depression. But the worst thing that happens in postpartum depression is support from family. The conclusion was postpartum depressive symptoms can affect exclusive breast milk because there are hormonal and mood changes that occur in the mother such as lack of appetite, sleep disturbances, anxiety, sensitivity so that they can interfere with the smoothness of breast milk.  

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

2020 ◽  
Vol 13 ◽  
pp. 251686572093214
Author(s):  
Valeska Stonawski ◽  
Jakob Roetner ◽  
Tamme W Goecke ◽  
Peter A Fasching ◽  
Matthias W Beckmann ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Depressive Symptoms ◽  
Small Sample Size ◽  
Child Outcomes ◽  
Depression Scale ◽  
Small Sample ◽  
Future Research ◽  
Functional Domain ◽  
Maternal Depressive Symptoms ◽  
Genome Wide

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.

scholarly journals Birth weight associations with psychiatric and physical health, cognitive function, and DNA methylation differences in an adult population

2019 ◽  
Author(s):  
Rebecca A. Madden ◽  
Daniel L. McCartney ◽  
Rosie M. Walker ◽  
Robert F. Hillary ◽  
Mairead L. Bermingham ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Birth Weight ◽  
Health Outcomes ◽  
Data Linkage ◽  
Meta Analysis ◽  
Adult Health ◽  
Adult Sample ◽  
Genome Wide ◽  
Plausible Mechanism ◽  
Weight Data

AbstractBackgroundThe Developmental Origins of Adult Disease (DOAD) theory predicts that prenatal and early life events shape adult health outcomes. Birth weight is a useful indicator of the foetal experience, and has been associated with multiple adult health outcomes. DNA methylation (DNAm) is one plausible mechanism behind the relationship of birth weight to adult health.MethodsThe Generation Scotland study allows data linkage to historic Scottish birth cohorts, and birth records held through the NHS Information and Statistics Division. Data linkage with these sources yielded a sample of 4, 710 individuals. Health measures were related to birth weight in regression models. An epigenome-wide association study (EWAS) was performed in a subgroup (n=1, 395), relating adult DNAm from whole blood to birth weight, with replication in an independent sample (n=362). Associations between birth weight and epigenetic clocks were also assessed.FindingsHigher birth weight was significantly associated with reduced incidence of depression and osteoarthritis, higher body mass index, and higher general intelligence (absolute standardised effect size range 0·04 to 0·30, p(FDR)<0·05). Meta-analysis of discovery and replication EWAS studies yielded one genome-wide significant CpG site (p=5·97×10−9), cg00966482. Significant associations between birth weight and Grim Age (p=0·0014) and DNAm-derived telomere length (p=3·3×10−4) are also described.InterpretationOur results demonstrate associations between birth weight and adult health outcomes, with particularly striking effects for depression risk. It also provides support for an association between birth weight and DNAm, describing the first significant EWAS site associated with birth weight in an adult sample.FundingWellcome Trust Strategic Award 104036/Z/14/ZResearch in ContextEvidence before this studyThe associations between birth weight and various adult health outcomes have been well established. DNA methylation is a plausible mechanism through which early life experiences may continue to affect health throughout the lifecourse; however, evidence for birth weight associations with DNA methylation in adulthood has not yet been robustly established. This is likely due to small sample sizes of previous samples, as well as the use of poor-quality birth weight data, such as binary ‘low/normal’ variables or retrospective self-report. Alternatively, work has attempted to describe the persistence into adulthood of DNA methylation at sites identified at birth.Added value of this studyWe investigated genome-wide differential DNA methylation patterns from whole blood using data linkage-derived, continuous birth weight data, in the largest reported adult sample (n=1, 395) with replication (n=362) and meta-analysis. Meta-analysis revealed one epigenome-wide significant CpG site, to our knowledge the first significant EWAS result reported for birth weight in a an adult sample. In addition, we found associations between birth weight and GrimAge and a DNA methylation-derived measure of telomere length, demonstrating accelerated biological ageing in lower birth weight individuals. Together, these results suggest differential methylation exists in adulthood related to birth weight, and this may be relevant to health and mortality.Implications of all the available evidenceAlthough CpG sites differentially methylated with birth weight at parturition may not remain so throughout life, the adult epigenome may still provide information on the impact of birth weight on health outcomes. The adult epigenome, therefore, may represent a useful archive of the foetal experience which results in birth weight variability, and this information may provide clinically useful information in mid-life.

scholarly journals Discovery of the first genome-wide significant risk loci for ADHD

2017 ◽  
Author(s):  
Ditte Demontis ◽  
Raymond K. Walters ◽  
Joanna Martin ◽  
Manuel Mattheisen ◽  
Thomas D. Als ◽  
...  
Keyword(s):  
Meta Analysis ◽  
Significant Risk ◽  
Behavioral Disorder ◽  
School Age Children ◽  
Loss Of Function ◽  
Clinical Interviews ◽  
Genome Wide ◽  
Common Genetic Variants ◽  
A Genome ◽  
Genomic Regions

AbstractAttention-Deficit/Hyperactivity Disorder (ADHD) is a highly heritable childhood behavioral disorder affecting 5% of school-age children and 2.5% of adults. Common genetic variants contribute substantially to ADHD susceptibility, but no individual variants have been robustly associated with ADHD. We report a genome-wide association meta-analysis of 20,183 ADHD cases and 35,191 controls that identifies variants surpassing genome-wide significance in 12 independent loci, revealing new and important information on the underlying biology of ADHD. Associations are enriched in evolutionarily constrained genomic regions and loss-of-function intolerant genes, as well as around brain-expressed regulatory marks. These findings, based on clinical interviews and/or medical records are supported by additional analyses of a self-reported ADHD sample and a study of quantitative measures of ADHD symptoms in the population. Meta-analyzing these data with our primary scan yielded a total of 16 genome-wide significant loci. The results support the hypothesis that clinical diagnosis of ADHD is an extreme expression of one or more continuous heritable traits.

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

Epigenomics ◽  
2020 ◽  
Author(s):  
Alexandra E Dereix ◽  
Rachel Ledyard ◽  
Allyson M Redhunt ◽  
Tessa R Bloomquist ◽  
Kasey JM Brennan ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Depressive Symptoms ◽  
Trait Anxiety ◽  
Cpg Island ◽  
Depression Scale ◽  
Maternal Anxiety ◽  
Anxiety And Depression ◽  
Pregnancy Anxiety ◽  
Glucocorticoid Receptor Gene ◽  
Island Shore

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.

Sign in / Sign up

Export Citation Format

Share Document