Epigenome-wide DNA methylation profiling in CBMCs
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE190908 | GEO | 2024/12/10
REPOSITORIES: GEO
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Project description:Background The timing and mechanisms of asthma inception remain imprecisely defined. Although epigenetic mechanisms likely contribute to asthma pathogenesis, little is known about their role in asthma inception. Objective To assess whether the trajectory to asthma begins already at birth and epigenetic mechanisms, specifically DNA methylation, contribute to asthma inception. Methods We used a combination of methyl binding protein-dependent DNA capture and microarrays to survey DNA methylation in cord blood mononuclear cells (CBMC) from 36 children (18 non-asthmatic, 18 asthmatic by age 9) from the Infant Immune Study (IIS), an unselected birth cohort closely monitored for asthma for a decade. SMAD3 methylation in IIS (n=60) and in two replication cohorts (The Manchester Asthma and Allergy Study, n=30, and the Childhood Origins of ASThma Study, n=28) was analyzed by bisulfite sequencing or Illumina 450K arrays. CBMC-derived IL-1b was measured by ELISA. Results Neonatal immune cells harbored 589 differentially methylated regions (DMRs) that distinguished IIS children who did and did not develop asthma by age 9. In all three cohorts, methylation in SMAD3, the most connected hub within the network of asthma-associated DMRs, was selectively increased in asthmatic children of asthmatic mothers and was associated with childhood asthma risk. Moreover, SMAD3 methylation in IIS neonates with maternal asthma was strongly and positively associated with neonatal production of IL-1b, an innate inflammatory mediator. Conclusions The trajectory to childhood asthma begins at birth and involves epigenetic modifications in immunoregulatory and pro-inflammatory pathways. Maternal asthma influences epigenetic mechanisms that contribute to the inception of this trajectory.
2017-04-13 | GSE85228 | GEO
Project description:Asthma is caused by a combination of poorly understood genetic and environmental factors. We found multiple markers on chromosome 17q21 to be strongly and reproducibly associated with childhood onset asthma in family and case-referent panels with a combined P < 10-12. In independent replication studies the 17q21 locus showed strong association with diagnosis of childhood asthma in 2,320 subjects from a cohort of German children (P = 0.0003) and in 3,301 subjects from the British 1958 Birth Cohort (P = 0.0005). We systematically evaluated the relationships between markers of the 17q21 locus and transcript levels of genes in EBV-transformed lymphoblastoid cell lines from children in the asthma family panel used in our association study. The SNPs associated with childhood asthma were consistently and strongly associated (P <10-22) in cis with transcript levels of ORMDL3, a member of a gene family that encode transmembrane proteins anchored in the endoplasmic reticulum. The results indicate that genetic variants regulating ORMDL3 expression are determinants of susceptibility to childhood asthma. Experiment Overall Design: Gene expression levels were evaluated in 404 children. We then evaluated the relationship between SNPs in the 17q21 region (which show association to asthma in the same children) with gene expression levels. See http://www.sph.umich.edu/csg/liang/asthma/
2007-11-09 | E-GEOD-8052 | biostudies-arrayexpress
Project description:Asthma is caused by a combination of poorly understood genetic and environmental factors. We found multiple markers on chromosome 17q21 to be strongly and reproducibly associated with childhood onset asthma in family and case-referent panels with a combined P < 10-12. In independent replication studies the 17q21 locus showed strong association with diagnosis of childhood asthma in 2,320 subjects from a cohort of German children (P = 0.0003) and in 3,301 subjects from the British 1958 Birth Cohort (P = 0.0005). We systematically evaluated the relationships between markers of the 17q21 locus and transcript levels of genes in EBV-transformed lymphoblastoid cell lines from children in the asthma family panel used in our association study. The SNPs associated with childhood asthma were consistently and strongly associated (P <10-22) in cis with transcript levels of ORMDL3, a member of a gene family that encode transmembrane proteins anchored in the endoplasmic reticulum. The results indicate that genetic variants regulating ORMDL3 expression are determinants of susceptibility to childhood asthma. Keywords: association study, global gene expression, asthma, ORMDL3
2007-07-01 | GSE8052 | GEO
Project description:Metagenomic and targeted meta-proteomics were used to investigate the mycobiome profile of the infant gut to identify proteins involved during atopic dermatitis manifestation in a Thai population-based birth cohort.
2021-09-14 | PXD027687 | JPOST Repository
Project description:Metaproteomics approach was used to investigate the microbial community and diversity of the infant gut to identify different key proteins with metabolic functional roles in the microbiomes of healthy and atopic dermatitis infants in a Thai population-based birth cohort.
2020-09-06 | PXD021324 | JPOST Repository
Project description:Genome wide DNA methylation profiling of umbilical cord blood DNA samples. The Illumina Infinium MethylationEPIC array was used to obtain DNA methylation profiles across approximately 850,000 CpGs. Samples included 470 cord blood samples from infants born to women in the Southampton Women's Survery (SWS) cohort, to examine the association between DNA methylation in the infant and aspects of health and disease in early and life and childhood.
2021-08-18 | GSE154915 | GEO
Project description:Severe LRIs are a major cause of infant/child hospitalization and a risk factors for asthma pathogenisis. Innate immune interactions with microbial pathogens, esp. in early life, underpin risk. We aimed to characterize cord blood mononuclear cell (CBMC) responses to activation of micriobial recognition receptors (TLRs 3, 4, & 7) and identify response pattern variations associated withsLRI susceptibility in infancy.
2022-08-24 | GSE184383 | GEO
Project description:Background: Asthma is common chronic inflammatory disease of the airways with a heterogenous clinical presentation. Individual differences in asthma susceptibility remain poorly understood, although genetics is thought to play a major role. Aim: To build a polygenic risk score (PRS) for asthma and determine whether predictive genetic variants can be epigenomically linked to specific pathophysiological mechanisms. Methods: PRSs were constructed using data from genome-wide association studies and performance was validated using data generated in the Rotterdam Study, a Dutch prospective cohort of 14,926 individuals. Outcomes used were asthma, childhood-onset asthma, adulthood-onset asthma, eosinophilic asthma and exacerbations. Chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-Seq) data from 14 primary cell types, including lung epithelial cells and T lymphocytes was used for epigenomic PRS partitioning. Results: All PRSs successfully predicted risk to develop asthma and related outcomes, with the strongest predictive power (2.42 odds ratios per PRS standard deviation, area under the curve of 0.736) achieved for childhood-onset asthma. PRSs allowed for stratification of the Rotterdam Study cohort into groups at low or high risk to develop asthma. PRS partitioning using genome-wide epigenomic profiles identified 5 clusters of variants within gene regulatory regions linked to specific asthma-relevant cells, genes and biological pathways. Conclusions: PRSs can predict whether individuals in a Dutch cohort developed asthma and asthma-related phenotypes, which is most effective for childhood-onset asthma. Importantly, we show that PRS partitioning based on epigenomics data dissects a genetic risk score into blocks of regulatory variants with differential predictive power, which likely represent distinct genetically driven disease pathways. These findings have potential implications for personalized risk mitigation and treatment strategies.
2024-07-03 | GSE245569 | GEO
Project description:These analyses set out to evaluate placental genomic and epigenomic signatures in newborns from the Extremely Low Gestational Age Newborns (ELGAN) cohort. Genome-wide mRNA, microRNA, and DNA methylation profiles were obtained from placenta samples collected at birth. Analyses were conducted to better understand placental molecular signatures and relate these to placental, maternal, infant, and later-in-life health indices.
2021-03-01 | GSE167885 | GEO