DNA methylation and gene expression differences at growth related genes correlate with birth weight.
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE36831 | GEO | 2012/03/29
SECONDARY ACCESSION(S): PRJNA157133
REPOSITORIES: GEO
Similar Datasets
Project description:This SuperSeries is composed of the following subset Series: GSE36812: Epigenome analysis of cord blood samples from newborns GSE36828: Genome-wide analysis of gene expression levels in placenta and cord blood samples from newborns babies GSE36829: Epigenome analysis of placenta samples from newborns GSE36852: Epigenome analysis of newborn placenta and cord blood samples Refer to individual Series
2012-03-28 | E-GEOD-36831 | biostudies-arrayexpress
Project description:BackgroundInfant birth weight is a complex quantitative trait associated with both neonatal and long-term health outcomes. Numerous studies have been published in which candidate genes (IGF1, IGF2, IGF2R, IGF binding proteins, PHLDA2 and PLAGL1) have been associated with birth weight, but these studies are difficult to reproduce in man and large cohort studies are needed due to the large inter individual variance in transcription levels. Also, very little of the trait variance is explained. We decided to identify additional candidates without regard for what is known about the genes. We hypothesize that DNA methylation differences between individuals can serve as markers of gene "expression potential" at growth related genes throughout development and that these differences may correlate with birth weight better than single time point measures of gene expression.MethodsWe performed DNA methylation and transcript profiling on cord blood and placenta from newborns. We then used novel computational approaches to identify genes correlated with birth weight.ResultsWe identified 23 genes whose methylation levels explain 70-87% of the variance in birth weight. Six of these (ANGPT4, APOE, CDK2, GRB10, OSBPL5 and REG1B) are associated with growth phenotypes in human or mouse models. Gene expression profiling explained a much smaller fraction of variance in birth weight than did DNA methylation. We further show that two genes, the transcriptional repressor MSX1 and the growth factor receptor adaptor protein GRB10, are correlated with transcriptional control of at least seven genes reported to be involved in fetal or placental growth, suggesting that we have identified important networks in growth control. GRB10 methylation is also correlated with genes involved in reactive oxygen species signaling, stress signaling and oxygen sensing and more recent data implicate GRB10 in insulin signaling.ConclusionsSingle time point measurements of gene expression may reflect many factors unrelated to birth weight, while inter-individual differences in DNA methylation may represent a "molecular fossil record" of differences in birth weight-related gene expression. Finding these "unexpected" pathways may tell us something about the long-term association between low birth weight and adult disease, as well as which genes may be susceptible to environmental effects. These findings increase our understanding of the molecular mechanisms involved in human development and disease progression.
| S-EPMC3359247 | biostudies-literature
Project description:The Developmental Origins of Health and Disease (DOHaD) 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. Through data linkage between Generation Scotland and historic Scottish birth cohorts, and birth records held through the NHS Information and Statistics Division, a sample of 1,757 individuals with available birth weight and DNAm data was derived. Epigenome-wide association studies (EWAS) were performed in two independently generated DNAm subgroups (nSet1 = 1,395, nSet2 = 362), relating adult DNAm from whole blood to birth weight. Meta-analysis yielded one genome-wide significant CpG site (p = 5.97x10-9), cg00966482. There was minimal evidence for attenuation of the effect sizes for the lead loci upon adjustment for numerous potential confounder variables (body mass index, educational attainment, and socioeconomic status). Associations between birth weight and epigenetic measures of biological age were also assessed. Associations between lower birth weight and higher Grim Age acceleration (p(FDR) = 3.6x10-3) and shorter DNAm-derived telomere length (p(FDR) = 1.7x10-3) are described, although results for three other epigenetic clocks were null. Our results provide support for an association between birth weight and DNAm both locally at one CpG site, and globally via biological ageing estimates.
| S-EPMC8216207 | biostudies-literature
Project description:Individuals born at low or high birth weight (BW) have elevated adiposity. The extent to which physical activity can mitigate this risk is unknown.The aim of this study was to determine if associations between BW and adiposity vary by self-reported moderate-to-vigorous physical activity (MVPA) among adolescents.We used data on adolescents in the National Health and Nutrition Examination Survey (1999-2006; 12-15 years; n?=?4064). Using gender-stratified linear regression, we modelled body mass index (BMI) and waist circumference (WC) z-scores as a function of low, normal and high BW, MVPA (weekly Metabolic Equivalent of Task hours) and MVPA*BW cross-product terms, adjusting for sociodemographics, diet and, in WC models, BMI.Among girls with low MVPA, those born with high BW had greater BMI than normal BW; this difference diminished with greater MVPA (coefficient [95% confidence interval]: low MVPA: 0.72 [0.29, 1.14]; high MVPA: -0.04 [-0.48, 0.39]; P for interaction?=?0.05). Among boys, MVPA did not modify the associations between BW and BMI. WC was unrelated to BW, regardless of MVPA.Findings suggest that effects of high BW in total adiposity can be more easily modified with MVPA in adolescent girls than in boys.
| S-EPMC4653090 | biostudies-literature
Project description:Study questionIs there a relation between ART and DNA methylation (DNAm) patterns in cord blood, including any differences between IVF and ICSI?Summary answerDNAm at 19 CpGs was associated with conception via ART, with no difference found between IVF and ICSI.What is known alreadyPrior studies on either IVF or ICSI show conflicting outcomes, as both widespread effects on DNAm and highly localized associations have been reported. No study on both IVF and ICSI and genome-wide neonatal DNAm has been performed.Study design, size, durationThis was a cross-sectional study comprising 87 infants conceived with IVF or ICSI and 70 conceived following medically unassisted conception. The requirement for inclusion in the study was an understanding of the Swedish language and exclusion was the use of donor gametes.Participants/materials, setting, methodsParticipants were from the UppstART study, which was recruited from fertility and reproductive health clinics, and the Born into Life cohort, which is recruited from the larger LifeGene study. We measured DNAm from DNA extracted from cord blood collected at birth using a micro-array (450k array). Group differences in DNAm at individual CpG dinucleotides (CpGs) were determined using robust linear models and post-hoc Tukey's tests.Main results and the role of chanceWe found no association of ART conception with global methylation levels, imprinted loci and meta-stable epialleles. In contrast, we identify 19 CpGs at which DNAm was associated with being conceived via ART (effect estimates: 0.5-4.9%, PFDR < 0.05), but no difference was found between IVF and ICSI. The associated CpGs map to genes related to brain function/development or genes connected to the plethora of conditions linked to subfertility, but functional annotation did not point to any likely functional consequences.Limitations, reasons for cautionWe measured DNAm in cord blood and not at later ages or in other tissues. Given the number of tests performed, our study power is limited and the findings need to be replicated in an independent study.Wider implications of the findingsWe find that ART is associated with DNAm differences in cord blood when compared to non-ART samples, but these differences are limited in number and effect size and have unknown functional consequences in adult blood. We did not find indications of differences between IVF and ICSI.Study funding/competing interest(s)E.W.T. was supported by a VENI grant from the Netherlands Organization for Scientific Research (91617128) and JPI-H2020 Joint Programming Initiative a Healthy Diet for a Healthy Life (JPI HDHL) under proposal number 655 (PREcisE Project) through ZonMw (529051023). Financial support was provided from the European Union's Seventh Framework Program IDEAL (259679), the Swedish Research Council (K2011-69X-21871-01-6, 2011-3060, 2015-02434 and 2018-02640) and the Strategic Research Program in Epidemiology Young Scholar Awards, Karolinska Institute (to A.N.I.) and through the Swedish Initiative for Research on Microdata in the Social And Medical Sciences (SIMSAM) framework grant no 340-2013-5867, grants provided by the Stockholm County Council (ALF-projects), the Strategic Research Program in Epidemiology at Karolinska Institutet and the Swedish Heart-Lung Foundation and Danderyd University Hospital (Stockholm, Sweden). The funders had no role in study design, data collection, analysis, decision to publish or preparation of the manuscript. The authors declare no competing interests.Trial registration numberN/A.
| S-EPMC7801794 | biostudies-literature
Project description:BackgroundThis study assessed the associations between nine differentially methylated regions (DMRs) of imprinted genes in DNA derived from umbilical cord blood leukocytes in males and females and (1) birth weight for gestational age z score, (2) weight-for-length (WFL) z score at 1 year, and (3) body mass index (BMI) z score at 3 years.MethodsWe conducted multiple linear regression in n = 567 infants at birth, n = 288 children at 1 year, and n = 294 children at 3 years from the Newborn Epigenetics Study (NEST). We stratified by sex and adjusted for race/ethnicity, maternal education, maternal pre-pregnancy BMI, prenatal smoking, maternal age, gestational age, and paternal race. We also conducted analysis restricting to infants not born small for gestational age.ResultsWe found an association between higher methylation of the sequences regulating paternally expressed gene 10 (PEG10) and anthropometric z scores at 1 year (β = 0.84; 95% CI = 0.34, 1.33; p = 0.001) and 3 years (β = 1.03; 95% CI = 0.37, 1.69; p value = 0.003) in males only. Higher methylation of the DMR regulating mesoderm-specific transcript (MEST) was associated with lower anthropometric z scores in females at 1 year (β = - 1.03; 95% CI - 1.60, - 0.45; p value = 0.001) and 3 years (β = - 1.11; 95% CI - 1.98, - 0.24; p value = 0.01). These associations persisted when we restricted to infants not born small for gestational age.ConclusionOur data support a sex-specific association between altered methylation and weight status in early life. These methylation marks can contribute to the compendium of epigenetically regulated regions detectable at birth, influencing obesity in childhood. Larger studies are required to confirm these findings.
| S-EPMC6025828 | biostudies-literature
Project description:BACKGROUND:Exposure to traffic pollution during fetal development has been associated with reduced fetal growth, and there is evidence to suggest that epigenetic mechanisms in the placenta in the form of variant DNA methylation may be a potential mechanism underlying this effect. OBJECTIVES:To examine the association between residential proximity to nearest major roadway, as a marker of traffic-related pollution, fetal growth and placental DNA methylation. METHODS:We obtained residential addresses, placenta samples, and demographic data from 471 women following delivery of term infants. Using generalized linear models we evaluated the association between living close to a major roadway (defined as living ?150m from a primary highway or primary road or ?50m from a secondary road) and fetal growth and DNA methylation of repetitive elements (LINE-1 and AluYb8). We evaluated epigenome-wide methylation in a subset of 215 women to further investigate specific variation in DNA methylation associated with proximity to major roadways. RESULTS:Living close to a major roadway was associated with a 175.9g (95% CI: -319.4, -32.5; p=0.016) lower birth weight, 1.8 (95% CI: 0.9, 3.8; p=0.09) times the odds of being small for gestational age, and 0.82 percentage points (95% CI: -1.57, -0.07; p=0.03) lower mean placental LINE-1 methylation levels in fully adjusted models. In epigenome-wide analyses, 7 CpG sites were significantly associated with residential proximity to major roadways. Additional adjustment for placental methylation did not attenuate the association between roadway proximity and birth weight. CONCLUSIONS:Living close to major roadways was associated with both lower fetal growth and significant placental epigenetic changes. However, the observed epigenetic changes appear insufficient to explain the observed association between roadway proximity and fetal growth.
| S-EPMC4913202 | biostudies-literature
Project description:Gestational age (GA) and birth weight have been implicated in the determination of long-term health. It has been hypothesized that changes in DNA methylation may mediate these long-term effects. We obtained DNA methylation profiles from cord blood and peripheral blood at ages 7 and 17 in the same children from the Avon Longitudinal Study of Parents and Children. Repeated-measures data were used to investigate changes in birth-related methylation during childhood and adolescence. Ten developmental phenotypes (e.g. height) were analysed to identify possible mediation of health effects by DNA methylation. In cord blood, methylation at 224 CpG sites was found to be associated with GA and 23 CpG sites with birth weight. Methylation changed in the majority of these sites over time, but neither birth characteristic was strongly associated with methylation at age 7 or 17 (using a conservative correction for multiple testing of P < 1.03 × 10(-7)), suggesting resolution of differential methylation by early childhood. Associations were observed between birth weight-associated CpG sites and phenotypic characteristics in childhood. One strong association involved birth weight, methylation of a CpG site proximal to the NFIX locus and bone mineral density at age 17. Analysis of serial methylation from birth to adolescence provided evidence for a lack of persistence of methylation differences beyond early childhood. Sites associated with birth weight were linked to developmental genes and have methylation levels which are associated with developmental phenotypes. Replication and interrogation of causal relationships are needed to substantiate whether methylation differences at birth influence the association between birth weight and development.
| S-EPMC4459393 | biostudies-literature
Project description:Low birth weight (LBW) is a major public health issue as it increases the risk of noncommunicable diseases throughout life. However, the genome-wide DNA methylation patterns of full-term LBW infants (FT-LBWs) are still unclear. This exploratory study aimed to analyze the DNA methylation differences in FT-LBWs compared with those in full-term normal birth weight infants (FT-NBWs) whose mothers were nonsmokers and had no complications. Initially, 702 Japanese women with singleton pregnancies were recruited. Of these, four FT-LBWs and five FT-NBWs were selected as references for DNA methylation analysis, and 862,260 CpGs were assessed using Illumina Infinium MethylationEPIC BeadChip. Gene ontology enrichment analysis was performed using DAVID v6.8 software to identify the biological functions of hyper- and hypomethylated DNA in FT-LBWs. 483 hyper-differentially methylated genes (DMGs) and 35 hypo-DMGs were identified in FT-LBW promoter regions. Hyper-DMGs were annotated to 11 biological processes; "macrophage differentiation" (e.g., CASP8), "apoptotic mitochondrial changes" (e.g., BH3), "nucleotide-excision repair" (e.g., HUS1), and "negative regulation of inflammatory response" (e.g., NLRP12 and SHARPIN). EREG was classified into "ovarian cumulus expansion" within the "organism growth and organization" category. Our data imply that LBW might be associated with epigenetic modifications, which regulate the immune system and cell maturation.
| S-EPMC7126402 | biostudies-literature
Project description:DNA methylation patterns differ among children and adults and play an unambiguous role in several disease processes, particularly cancers. The origin of these differences is inadequately understood, and this is a question of specific relevance to childhood and adult cancer.DNA methylation levels at 26,485 autosomal CpGs were assayed in 201 newborns (107 African American and 94 Caucasian). Nonparametric analyses were performed to examine the relation between these methylation levels and maternal parity, maternal age, newborn gestational age, newborn gender, and newborn race. To identify the possible influences of confounding, stratification was performed by a second and third variable. For genes containing CpGs with significant differences in DNA methylation levels between races, analyses were performed to identify highly represented gene ontological terms and functional pathways.13.7% (3623) of the autosomal CpGs exhibited significantly different levels of DNA methylation between African Americans and Caucasians; 2% of autosomal CpGs had significantly different DNA methylation levels between male and female newborns. Cancer pathways, including four (pancreatic, prostate, bladder, and melanoma) with substantial differences in incidence between the races, were highly represented among the genes containing significant race-divergent CpGs.At birth, there are significantly different DNA methylation levels between African Americans and Caucasians at a subset of CpG dinucleotides. It is possible that some of the epigenetic precursors to cancer exist at birth and that these differences partially explain the different incidence rates of specific cancers between the races.
| S-EPMC3429933 | biostudies-literature