MARBLES (Markers of Autism Risk in Babies: Learning Early Sign) Enriched Cohort Study:Internal Metabolomic Biomarker Exposome and Development Disorders (IMBEDD)
Ontology highlight
ABSTRACT:
ORGANISM(S): Human Homo Sapiens
TISSUE(S): Blood
DISEASE(S): Autism
SUBMITTER: 
Karan Uppal
PROVIDER: ST001209 | MetabolomicsWorkbench | Wed Jul 03 00:00:00 BST 2019
REPOSITORIES: MetabolomicsWorkbench
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| mwtab | Other |
Items per page: 5 1 - 1 of 1 |
Similar Datasets
Project description:This project aims to identify internal biomarkers of drug, food and microbial exposures associated to Autism Spectrum Disorder (ASD) and neurodevelopmental outcomes in an enriched-risk cohort. Using targeted and untargeted internal exposome approaches to identify exposures in maternal blood and child cord blood, internal metabolomics biomarkers will be associated with related exposures and also associated with ASD.
2019-06-11 | ST001193 | MetabolomicsWorkbench
Project description:This project aims to evaluate the internal environmental exposome of mother/fetus pairs within the PARENTs cohort, assessing a wide range of biomarkers/internal exposure measures for environmental toxins including air pollutants. Focusing on advanced imaging data on placental development and robust, clinically-confirmed birth outcomes, this a hypothesis-generating, untargeted pilot metabolomics study aims to identify potential predictors of placental insufficiencies and adverse birth outcomes. Measurements of exposures which include residential, occupational, and behavioral exposures, along with personalized air pollution measures, will help us in identifying related metabolomics patterns.
2020-02-20 | ST001335 | MetabolomicsWorkbench
Project description:Autism spectrum disorder (ASD) is a neurodevelopmental disorder that affects more than 1% of children in the USA. ASD risk is thought to arise from both genetic and environmental factors, with the perinatal period as a critical window. Understanding early transcriptional changes in ASD would assist in clarifying disease pathogenesis and identifying biomarkers. However, little is known about umbilical cord blood gene expression profiles in babies later diagnosed with ASD compared to non-typically developing and non-ASD (Non-TD) or typically developing (TD) children. Genome-wide transcript levels were measured by Affymetrix Human Gene 2.0 array in RNA from cord blood samples from both the Markers of Autism Risk in Babies-Learning Early Signs (MARBLES) and the Early Autism Risk Longitudinal Investigation (EARLI) high-risk pregnancy cohorts that enroll younger siblings of a child previously diagnosed with ASD. Younger siblings were diagnosed based on assessments at 36 months, and 59 ASD, 92 Non-TD, and 120 TD subjects were included. Using both differential expression analysis and weighted gene correlation network analysis, gene expression between ASD and TD, and between Non-TD and TD, was compared within each study and via meta-analysis. While cord blood gene expression differences comparing either ASD or Non-TD to TD did not reach genome- wide significance, 172 genes were nominally differentially expressed between ASD and TD cord blood (log2(fold change) > 0.1, p < 0.01). These genes were significantly enriched for functions in xenobiotic metabolism, chromatin regulation, and systemic lupus erythematosus (FDR q < 0.05). In contrast, 66 genes were nominally differentially expressed between Non-TD and TD, including 8 genes that were also differentially expressed in ASD. Gene coexpression modules were significantly correlated with demographic factors and cell type proportions. ASD-associated gene expression differences identified in this study are subtle, as cord blood is not the main affected tissue, it is composed of many cell types, and ASD is a heterogeneous disorder. This is the first study to identify gene expression differences in cord blood specific to ASD through a meta- analysis across two prospective pregnancy cohorts. The enriched gene pathways support involvement of environmental, immune, and epigenetic mechanisms in ASD etiology.
2019-10-25 | GSE123302 | GEO
Project description:Deleterious genetic variants in POGZ, which encodes the chromatin regulator Pogo Transposable Element with ZNF Domain protein, are strongly associated with autism spectrum disorder (ASD). Although it is a high confidence ASD risk gene, the neurodevelopmental functions of POGZ remain unclear. Here we reveal the genomic binding of POGZ in the developing forebrain at euchromatic loci and gene regulatory elements (REs). We profile chromatin accessibility and gene expression in Pogz-/- mice and show that POGZ promotes the active chromatin state and transcription of clustered synaptic genes. We further demonstrate that POGZ forms a nuclear complex and co-occupies loci with ADNP, another high-confidence ASD risk gene, and provide evidence that POGZ regulates other neurodevelopmental disorder risk genes as well. Our results reveal a neurodevelopmental function of an ASD risk gene and identify molecular targets that may elucidate its function in ASD.
2021-11-05 | GSE187010 | GEO
Project description:A causal role of mutations in genes encoding for multiple general transcription factors in neurodevelopmental disorders including autism suggested that alterations at the global level of gene expression regulation might also relate to disease risk in sporadic cases of autism. This premise can be tested by evaluating for global changes in the overall distribution of gene expression levels. For instance, in mice, we recently showed that variability in hippocampal-dependent behaviors was associated with variability in the pattern of the overall distribution of gene expression levels, as assessed by variance in the distribution of gene expression levels in the hippocampus. We hypothesized that a similar change in the variance in gene expression levels might be found in children with autism. Gene expression microarrays covering greater than 47,000 unique RNA transcripts were done on purified RNA from peripheral blood lymphocytes of children with autism (n=82) and controls (n=64). The variance in the distribution of gene expression levels from each microarray was compared between groups of children. Also tested was whether a risk factor for autism, increased paternal age, was associated with variance in the overall distribution of gene expression levels. A decrease in the variance in the distribution of gene expression levels in peripheral blood lymphocytes (PBL) was associated with the diagnosis of autism and a risk factor for autism, increased paternal age. Traditional approaches to microarray analysis of gene expression suggested a possible mechanism for decreased variance in gene expression. Gene expression pathways involved in transcriptional regulation were down-regulated in the blood of children with autism and children of older fathers. Thus, results from global and gene specific approaches to studying microarray data were complimentary and supported the hypothesis that alterations at the global level of gene expression regulation are related to autism and increased paternal age. Regulation of transcription, thus, represents a possible point of convergence for multiple etiologies of autism and other neurodevelopmental disorders.
2011-10-09 | GSE25507 | GEO
Project description:MicroRNA biomarkers in blood for Autism spectrum disorder
| PRJNA352680 | ENA
Project description:Epigenetic changes such as DNA cytosine methylation modulate gene function across brain and are implicated in the pathophysiology of neurodevelopmental disorders including schizophrenia and autism. Epigenetic changes can be caused by environmental exposures such as inflammation, and may at least partly explain why prenatal exposure to inflammation increase risk of neurodevelopmental disorders. We used an MIA mouse model to investigate the postnatal epigenetic changes associated with exposure to the viral analogue PolyI:C. The effect of dietary supplement with omega-3 polyunsaturated fatty acids (PUFA) on exposed mice was also examined. Methylation was estimated genome-wide across gene regulatory regions. Widespread epigenetic changes were observed following exposure to inflammation during prenatal life. The differentially methylated gene set was enriched for genes involved in nervous system development and function. Omega-3 intervention modified the epigenetic profile, including a number of genes which were affected by MIA. These experiments indicate that environmental and genetic risk factors modulate similar biological pathways that are associated with neurodevelopmental disorders.
2019-08-15 | GSE102942 | GEO
Project description:Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social communication deficits and repetitive behaviors. MicroRNAs (miRNAs) have been recently recognized as potential biomarkers of ASD as they are dysregulated in various tissues of individuals with ASD. However, it remains unclear whether miRNA expression is altered in individuals with high-functioning ASD. Here, we investigated the miRNA expression profile in peripheral blood from adults with high-functioning ASD, and age and gender-matched healthy controls. Our findings may provide insights regarding the molecular clues for recognizing high-functioning ASD.
2020-05-03 | GSE89596 | GEO
Project description:Although autism spectrum disorder (ASD) is among the most heritable of neurodevelopmental disorders, the rapidly rising prevalence of ASD suggests that environmental factors may interact with genetic risk for ASD. Environmental factors may impact both gene expression and phenotypes in ASD through epigenetic modifications that, in turn, could lead to intergenerational effects influencing risk for ASDs. Endocrine disrupting compounds (EDCs), such as the long-lived organochlorines, are of particular interest with respect to risk for autism because of their ability to interfere with sex hormones that have been implicated in the regulation of RORA, a dysregulated gene in ASD that is a master regulator of many other ASD risk genes. The specific aims of this study are to: 1) investigate whether high versus low exposures to the persistent organochlorine 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE) are associated with differentially methylated regions (DMRs) in sperm from a Faroese cohort whose natural diet of pilot whale meat and blubber exposes them to higher than average levels of organic pollutants; 2) determine if genes associated with DDE DMRs are enriched for ASD risk genes; 3) identify pathways and functions over-represented among genes associated with DMRs. Whole genome bisulfite sequencing (WGBS) was used to identify genome-wide DMRs in sperm from individuals divided by high and low exposure levels. Gene ontology and pathway analyses were used to determine enrichment in functional relationships to ASD. Genes in DMRs not only could discriminate between high and low exposures to DDE, but also were enriched in autism risk genes. Gene ontology and pathway analyses of these genes show significant enrichment for neurodevelopmental processes frequently impacted by ASD. Results of this study show that elevated exposure to certain organochlorines is associated with genome-wide DNA methylation patterns in sperm affecting genes involved in neurological functions and developmental disorders, including ASD.
2022-08-31 | GSE165915 | GEO
Project description:Micronutrient deficiencies and environmental exposures have been to known to adversely impact brain and nervous system functions in adults and children worldwide. However, few studies have examined the short and long-term impact of these risk factors on neurodevelopmental outcomes in children in low-income countries, where the effects are likely to be more pronounced due to limited resources for monitoring and insufficient regulations. Biological risk factors of relevance include micronutrient deficiencies such as zinc and exposure to heavy metals such as lead and mercury. Studies have suggested an association between neurodevelopmental impairment and micronutrient deficiency as well as exposure to a number of heavy metals and environmental toxins. Moreover, findings also suggest that risk factors for adverse developmental outcomes that are independently significant may have the potential for causing cumulative increases in adverse effects. In Sub-Saharan Africa, severe malaria is a leading risk factor for long-term neurocognitive impairment in children. Zinc deficiency or exposure to heavy metals could influence risk of severe malaria, modify the risk of neurocognitive impairment in children with severe malaria, or independently affect risk of neurocognitive impairment. Untargeted analyses for potential environmental exposures or metabolomic changes in children with cerebral malaria vs. without cognitive impairment or in children with higher vs. lower cognitive scores, could also identify new risk factors for neurodevelopmental impairment in Ugandan children with cerebral malaria.In our completed study in Kampala, we assessed neurologic and developmental impairment in children with cerebral malaria [CM] or severe malarial anemia [SMA], as compared to health community children from the same extended household as the children with CM or SMA. As an extension of this study, we are interested in determining levels of micronutrients such as zinc in the population, and in addition, determining exposure levels of heavy metals (lead, mercury, copper, manganese etc.) in samples collected from children with severe malaria and community controls. The primary hypotheses of this study is that nutrient deficiencies or exposure to heavy metals influence short and long term neurocognitive outcomes in healthy community children and in children with severe malaria, and that children with cerebral malaria have specific metabolomic changes that relate to long-term neurocognitive impairment. The specific aims of our study are:Aim 1: To determine levels of zinc, heavy metals, and biomarkers associated with inflammation in children presenting with different forms of severe malaria (SM) and in healthy community children (CC). The working hypothesis of this aim is that 1) children with SM will have lower zinc levels compared to CC; 2) children with SM will present with higher toxic metal exposure and higher levels of biomarkers associated with inflammation than CC.Aim 2: To investigate how micronutrient deficiency, toxic metal exposure and inflammatory biomarkers affect short and long term neurodevelopmental outcomes and growth in children with severe malaria and community children (CC).The working hypothesis of this aim is that the lower levels of zinc, and presence of toxic metals in high concentrations will independently contribute to worsening neurodevelopmental outcomes and worsening growth over time in children with severe malaria and in community children. An alternate hypothesis is that micronutrient deficiency, toxic metal exposure and inflammatory states may interact with each other and with severe malaria to produce greater neurodevelopmental impairment, i.e., that the contribution is not independent but interactive.Aim 3: To determine whether the CSF metabolome differs according to level of neurodevelopmental impairment in children with cerebral malaria. The working hypothesis of this aim is that neurodevelopmental impairment in children with cerebral malaria is associated with changes in the CSF metabolome.
2017-09-27 | ST000877 | MetabolomicsWorkbench