Determining gestational age using genome methylation profile
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE109538 | GEO | 2019/07/18
REPOSITORIES: GEO
Similar Datasets
Project description:All subjects were recruited at Centennial Women?s Hospital and the Perinatal Research Center in Nashville, TN beginning in 2003. Pregnant women were enrolled during their first clinical visit after obtaining informed consent as described previously. Demographic and clinical data specific to the fetus was collected from clinical records. Gestational age of the neonate was determined by maternal reporting of the last menstrual period and corroboration by ultrasound dating. Accurate knowledge of gestational age (GA) is essential for proper monitoring and care of neonates. However, accurate GA measures are often not available. DNA methylation has previously been shown to associate with GA, and has been used to accurately predict chronological age in adults. In the current study, we examine whether DNA methylation in cord blood can be used to predict gestational age at birth. Results: We found that GA can be accurately predicted from DNA methylation of neonatal cord blood and blood spot samples (DNAm GA), using 148 CpG sites selected through elastic net regression in six training datasets (N=207). We evaluated predictive accuracy in six testing datasets (N=1,202), and found that the accuracy of DNAm GA meets or exceeds accuracy of gestational age estimates based on established methods. We also found an increased DNAm GA, relative to clinical GA, was associated with increased birthweight percentile (p=.00057), adjusting for GA, sex, and ancestry, suggesting that DNAm GA could represent developmental age more accurately than clinical estimates of GA. Conclusions: Further development of this predictor could provide a method of accurate neonatal estimation of GA for use in resource-limited populations, or in cases where GA cannot be estimated clinically. When clinical estimates are available, the predictor can be used to test hypotheses related to developmental age and other early life circumstances, and may provide increased accuracy beyond clinical estimates. 36 Umbilical cord blood samples were collected in EDTA tubes soon after placental delivery. Blood samples were centrifuged at 3,000 RPM to separate plasma, and buffy coats were aliquoted and stored at -80oC. DNA was extracted using the DNeasy Kit (Qiagen). DNA methylation was interrogated for each sample using the HumanMethylation450 BeadChip (Illumina).
2016-03-11 | E-GEOD-79056 | biostudies-arrayexpress
Project description:All subjects were recruited at Centennial Women?s Hospital and the Perinatal Research Center in Nashville, TN beginning in 2003. Pregnant women were enrolled during their first clinical visit after obtaining informed consent as described previously. Demographic and clinical data specific to the fetus was collected from clinical records. Gestational age of the neonate was determined by maternal reporting of the last menstrual period and corroboration by ultrasound dating. Accurate knowledge of gestational age (GA) is essential for proper monitoring and care of neonates. However, accurate GA measures are often not available. DNA methylation has previously been shown to associate with GA, and has been used to accurately predict chronological age in adults. In the current study, we examine whether DNA methylation in cord blood can be used to predict gestational age at birth. Results: We found that GA can be accurately predicted from DNA methylation of neonatal cord blood and blood spot samples (DNAm GA), using 148 CpG sites selected through elastic net regression in six training datasets (N=207). We evaluated predictive accuracy in six testing datasets (N=1,202), and found that the accuracy of DNAm GA meets or exceeds accuracy of gestational age estimates based on established methods. We also found an increased DNAm GA, relative to clinical GA, was associated with increased birthweight percentile (p=.00057), adjusting for GA, sex, and ancestry, suggesting that DNAm GA could represent developmental age more accurately than clinical estimates of GA. Conclusions: Further development of this predictor could provide a method of accurate neonatal estimation of GA for use in resource-limited populations, or in cases where GA cannot be estimated clinically. When clinical estimates are available, the predictor can be used to test hypotheses related to developmental age and other early life circumstances, and may provide increased accuracy beyond clinical estimates.
2016-03-11 | GSE79056 | GEO
Project description:In 1990, David Barker proposed that prenatal nutrition is directly linked to adult cardiovascular disease. Since then, the relationship between adult cardiovascular risk, metabolic syndrome and birth weight has been widely documented. Here we used the TruSeq Methyl Capture EPIC platform to compare the methylation patterns in cord blood from large for gestational age (LGA), small for gestational age (SGA) and adequate for gestational age/Control (AGA/Ctl) newborns. We found several differentially methylated CpGs (DMCs) and differentially methylated regions (DMRs) between LGA, SGA and AGA groups. A system biology approach identified several biological processes significantly enriched with genes in association with DMCs including Regulation of transcription, Regulation of epinephrine secretion, Norepinephrine biosynthesis, Receptor transactivation, Forebrain regionalization and several terms related with kidney and cardiovascular development. Gene ontology analysis of the genes in association with the DMRs identified several significantly enriched biological processes related with kidney development including Mesonephric duct development and Nephron tubule development. Furthermore, our dataset identified several DNA methylation markers enriched at gene networks involved in biological pathways and rare diseases of the cardiovascular system, kidneys and metabolism. Our study identified several DMCs/DMRs in association with fetal growth patterns. The use of cord blood as material for the identification of DNA methylation biomarkers gives us the possibility to perform follow up studies on the same patients as they enter childhood and puberty. These studies will not only help us understand how the methylome responds to continuum postnatal growth but also link early alterations of the DNA methylome with later clinical markers of growth and metabolic fitness.
2023-07-26 | GSE238155 | GEO
Project description:Maternal whole blood colected longitudinally were profiled using Affymetrix Human Transcriptome Arrays to evaluate prediction of gestational age in normal and complicated pregnancies and predict preterm birth. LMP is the date at the last menstrual period. Oper_LMP is the date at the last menstrual period with eventual adjustment based on ultrasound determination. Gestational age (GA) (weeks) is defined as (Date at sample - Oper_LMP)/7. For control pregnancies, SubGroup defines those with spontaneous labor at term (TL) as opposed with those delivered by cesarean section (TNL). Train is 1 if the sample was used in sub-challenge 1 in the training set as opposed to test set (0). D2 is 1 if the sample was used in the 2 interval prediction scenario, and if yes, it was assigned to the interval given by column D2Interval. D3 is 1 if the sample was used in the 3 interval prediction scenario, and if yes, it was assigned to the interval given by column D3Interval. DiagnosisGA is the gestational age at diagnosis with any disease indicated by the Group variable, and it is set to NA for normal pregnancies.
2021-05-24 | GSE149437 | GEO
Project description:The impact of healthy aging on molecular programming of immune cells is poorly understood. Here, we report comprehensive characterization of healthy aging in human classical monocytes, with a focus on epigenomic, transcriptomic, and proteomic alterations, as well as the corresponding proteomic and metabolomic data for plasma, using healthy cohorts of 20 young and 20 older males (~27 and ~64 years old on average). For each individual, we performed eRRBS-based DNA methylation profiling, which allowed us to identify a set of age-associated differentially methylated regions (DMRs) – a novel, cell-type specific signature of aging in DNA methylome. Hypermethylation events were associated with H3K27me3 in the CpG islands near promoters of lowly-expressed genes, while hypomethylated DMRs were enriched in H3K4me1 marked regions and associated with age-related increase of expression of the corresponding genes, providing a link between DNA methylation and age-associated transcriptional changes in primary human cells.
2022-02-16 | PXD021821 | Pride
Project description:Umbilical cord blood was collected from live deliveries at the Athens Regional Midwifery Clinic. Neonatal sex, race and gestational age was obtained by review of the delivery records.
2016-04-19 | GSE80310 | GEO
Project description:Objective: To explore the characteristics and underlying molecular mechanisms of genome-scale expression profiles of women with- or without- gestational diabetes mellitus and their offspring. Materials and Methods: We recruited a group of 21 pregnant women with gestational diabetes mellitus (GDM) and 20 healthy pregnant women as controls. For each pregnant women, RRBS were performed using the placenta and paired neonatal umbilical cord blood specimens. Differentially methylated regions (DMRs) were identified. Then, functional enrichment analysis was performed to differential methylated genes (DMGs) separately or interactively in placenta and umbilical cord blood. Results: Through the comparison of GDM and healthy samples, 2779 and 141 DMRs were identified from placenta and umbilical cord blood, respectively. Functional enrichment analysis showed that the placenta methylation and expression profiles of GDM women mirrored the molecular characteristics of “type II diabetes” and “insulin resistance”. Methylation-altered genes in umbilical cord blood were associated with pathways “type II diabetes” and “cholesterol metabolism”. DMGs illustrated significant overlaps among placenta and umbilical cord blood samples, and the overlapping DMGs were associated with cholesterol metabolism. Conclusions: Our research demonstrated the epigenomic alternations of GDM mothers and offspring. Our findings emphasized the importance of epigenetic modifications in the communication between pregnant women with GDM and offspring, and provided reference for the prevention, control, treatment, and intervention of perinatal deleterious events of GDM and neonatal complications.
2022-05-31 | GSE203169 | GEO
Project description:BACKGROUND: Babies born at lower gestational ages or smaller birthweights have a greater risk of poorer health in later life. Both the causes of these sub-optimal birth outcomes and the mechanism by which the effects are transmitted over decades are the subject of extensive study. We investigated whether a transcriptomic signature of either birthweight or gestational age could be detected in umbilical cord RNA. METHODS: The gene expression patterns of 32 umbilical cords from Singaporean babies of Chinese ethnicity across a range of birthweights (BW, 1698-4151g) and gestational ages (GA, 35-41 weeks) were determined. We confirmed the differential expression pattern by gestational age for 12 genes in a series of 127 umbilical cords of Chinese, Malay and Indian ethnicity. RESULTS: We found that the transcriptome is substantially influenced by gestational age; but less so by birthweight. We show that some of the expression changes dependent on gestational age are enriched in signal transduction pathways, such as Hedgehog and in genes with roles in cytokine signalling and angiogenesis. We show that some of the gene expression changes we report are reflected in the epigenome. CONCLUSIONS: We studied the umbilical cord which is peripheral to disease susceptible tissues. The results suggest that soma-wide transcriptome changes, preserved at the epigenetic level, may be a mechanism whereby birth outcomes are linked to the risk of adult metabolic and arthritic disease and suggest that greater attention be given to the association between premature birth and later disease risk.
2012-09-24 | GSE37100 | GEO
Project description:Preterm birth is a significant clinical problem and an enormous burden on society, affecting one in eight pregnant women and their newborns. Despite decades of research, its pathogenesis remains unclear. Many studies have shown that preterm birth is associated with health risks across the later life course. The “fetal origins” hypothesis postulates that adverse intrauterine exposures are associated with later disease susceptibility. Our recent studies have focused on the placental epigenome at term. We extended these studies to genome-wide placental DNA methylation across a wide range of gestational ages. We applied methylation dependent immunoprecipitation/DNA sequencing (MeDIP-seq) to 9 placentas with gestational age from 25 weeks to term to identify differentially methylated regions (DMRs). Enrichment analysis revealed 427 DMRs with nominally significant differences in methylation between preterm and term placentas (p<0.01) and 21 statistically significant DMRs after multiple comparison correction (FDR p<0.05), of which 62% were hypo-methylated in preterm placentas vs term placentas. The majority of DMRs were in distal intergenic regions and introns. Significantly enriched pathways identified by Ingenuity Pathway Analysis (IPA) included Citrulline-Nitric Oxide Cycle and Fcy Receptor Mediated Phagocytosis in macrophages. The DMR gene set overlapped placental gene expression data, genes and pathways associated evolutionarily with preterm birth. These studies form the basis for future studies on the epigenetics of preterm birth, "fetal programming” and the impact of environment exposures on this important clinical challenge.
2018-09-26 | GSE120458 | GEO
Project description:Preterm or small for gestational age (SGA) infants are to be at high risk of noncommunicable diseases in adolescence, because they are exposed to hypoxia and malnutrition in and ex utero during perinatal period. Epigenetics could be one of the most important mechanisms of DOHaD.In the field of premature babies, previous studies investigated the methylation alterations related to gestational age and birthweight by using cord blood samples. In the field of preterm or SGA babies, there were few EWAS studies that examine whether methylation changes relate to RNA expression using cord blood samples, and the interpretation of postnatal blood methylation were different by studies.The objective is to investigate the epigenetic alterations associated with preterm birth and SGA by using methylation and expression microarray, and to explore the epigenetic changes which may persist after birth.
2021-02-09 | GSE110828 | GEO