Infant Circulating MicroRNAs as Biomarkers of Effect in Fetal Alcohol Spectrum Disorders
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA689559 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Infant plasma miRNAs were isolated at 2 weeks and 6.5 months of age from prenatal alcohol exposed and control infants
2021-01-14 | GSE164209 | GEO
Project description:Kids First: Genetic Basis of Fetal Alcohol Spectrum Disorders
| PRJNA760564 | ENA
Project description:Kids First: Genetic Basis of Fetal Alcohol Spectrum Disorders
| PRJNA760565 | ENA
Project description:Prenatal alcohol exposure (PAE) can result in cognitive and behavioral disabilities and growth deficits. Because alcohol-related neurobehavioral deficits may occur in the absence of overt dysmorphic features or growth deficits, there is a need to identify biomarkers of PAE that can predict neurobehavioral impairment. In this study, we assessed infant plasma extracellular, circulating miRNAs (exmiRNAs) obtained from a heavily exposed Cape Town cohort to determine whether these can be used to predict PAE-related growth restriction and cognitive impairment. PAE, controlling for smoking as a covariate, altered 27% of expressed exmiRNAs with clinically-relevant effect sizes (Cohen's d ≥ 0.4). Moreover, at 2 weeks, PAE increased correlated expression of exmiRNAs across chromosomes, suggesting potential co-regulation. In confirmatory factor analysis, the variance in expression for PAE-altered exmiRNAs at 2 weeks and 6.5 months was best described by three-factor models. Pathway analysis found that factors at 2 weeks were associated with (F1) cell maturation, cell cycle inhibition, and somatic growth, (F2) cell survival, apoptosis, cardiac development, and metabolism, and (F3) cell proliferation, skeletal development, hematopoiesis, and inflammation, and at 6.5 months with (F1) neurodevelopment, neural crest/mesoderm-derivative development and growth, (F2) immune system and inflammation, and (F3) somatic growth and cardiovascular development. Factors F3 at 2 weeks and F2 at 6.5 months partially mediated PAE-induced growth deficits, and factor F3 at 2 weeks partially mediated effects of PAE on infant recognition memory at 6.5 months. These findings indicate that infant exmiRNAs can help identify infants who will exhibit PAE-related deficits in growth and cognition.
| S-EPMC7809131 | biostudies-literature
Project description:Learning disabilities are hallmarks of congenital conditions caused by prenatal exposure to harmful agents. This is particularly true for patients suffering from Fetal Alcohol Spectrum Disorders (FASD) who exhibit a wide range of cognitive deficiencies including impaired motor skill development. While these effects have been well characterized, the molecular effects that bring about these behavioral consequences remain to be determined. We have previously found that the acute molecular responses to alcohol in the embryonic brain are stochastic, varying among neural progenitor cells. However, the pathophysiological consequences stemming from these heterogeneous responses remain unknown. Here we show that acute responses to alcohol in progenitor cells lead to altered gene expression in their descendant neurons at the single-cell level. Among the altered genes, we found that an increase of the calcium-activated potassium channel Kcnn2 in subset neurons in the motor cortex correlates with motor skill learning deficits in the mouse model of FASD. We further show that postnatal blocking of Kcnn2 improves these learning deficits. These results propose Kcnn2 blockers as a novel intervention for learning disabilities in FASD and possibly for other neurocognitive conditions.
2021-08-30 | GSE141714 | GEO
Project description:Prenatal alcohol exposure is the leading preventable cause of behavioural and cognitive deficits, which may affect between 2-5% of children in North America. While the underlying mechanisms of alcohol’s effects on development remain relatively unknown, emerging evidence implicates epigenetic mechanisms in mediating the range of symptoms observed in children with Fetal Alcohol Spectrum Disorder (FASD). Thus, we investigated the effects of prenatal alcohol exposure on genome-wide DNA methylation in the NeuroDevNet FASD cohort, the largest cohort of human FASD samples to date. Genome-wide DNA methylation patterns of buccal epithelial cells were analyzed using the Illumina HumanMethylation450 array on a Canadian cohort of 206 children (110 FASD and 96 controls). Genotyping was performed in parallel using the Infinium HumanOmni2.5-Quad v1.0 BeadChip. After correcting for the effects of genetic background, 658 significantly differentially methylated sites between FASD cases and controls remained, with 41 displaying differences in beta greater than 5%. Furthermore, 203 differentially methylated regions containing 2 or more CpGs were also identified, overlapping with 167 different genes. The majority of differentially methylated genes were highly expressed in samples from the Allen Brain Atlas, which showed high correlations with buccal cell DNA methylation patterns. Furthermore, over-representation analysis of the up-methylated genes displayed a significant enrichment for neurodevelopmental processes and diseases, such as anxiety, epilepsy, and autism spectrum disorders. These findings suggest that prenatal alcohol exposure is associated with distinct DNA methylation patterns in children and adolescents, raising the possibility of an epigenetic biomarker of FASD.
2017-04-13 | GSE80261 | GEO
Project description:Genetics of Epilepsy and Cognitive Disorders: Autism Spectrum Disorders Study
| PRJNA213481 | ENA
Project description:The Illumina Human Omni2.5 array is a high resolution microarray platform for studying copy number variations in the human genome. It is widely being used in both clinical and research settings for identifying causative variants as well as interrogating the genome for benign variants. We employed this platform to investigate the risk factor CNVs in 95 individuals diagnosed with Fetal alcohol spectrum syndrome (FASD). We also examined 87 age-matched individuals with no symptoms of FASD or any neurodevelopmental disorders. We compared their CNVs to those of 10,851 population controls, in order to identify rare CNVs (<0.1% frequency) that might be relevant to FASD.
2018-11-21 | GSE102650 | GEO
Project description:Fetal alcohol spectrum disorders (FASD) are a group of neurodevelopmental disorders caused by ethanol exposure in utero, which can result in neurocognitive and behavioral impairments, growth defects, and craniofacial anomalies. FASD affects up to 1-5% of school-aged children in the United States, and there is currently no cure. The underlying mechanisms involved in ethanol teratogenesis remain elusive and need greater understanding to develop and implement effective therapies. Using a third trimester human equivalent postnatal mouse model of FASD, we evaluate the transcriptomic changes induced by ethanol exposure in the cerebellum on P5 and P6, after only 1 or 2 days of ethanol exposure, with the goal of shedding light on the transcriptomic changes induced early during the onset and development of FASD. We have highlighted key pathways and cellular functions altered by ethanol exposure, which include pathways related to immune function and cytokine signaling as well as the cell cycle. Additionally, we found that ethanol exposure resulted in an increase in transcripts associated with a neurodegenerative microglia phenotype, and acute- and pan-injury reactive astrocyte phenotypes. Mixed effects on oligodendrocyte lineage cell associated transcripts and cell cycle associated transcripts were observed. These studies help to elucidate the underlying mechanisms that may be involved with the onset of FASD and provide further insights that may aid in identifying novel targets for interventions and therapeutics.
2023-03-07 | GSE226532 | GEO
Project description:Analysis of methylomic alternations related with alcohol use disorders (AUD). The hypothesis is that chronic alcohol consumption might alter genome-wide DNA methylation patterns. The results suggest that differential DNA methylation might be invovled in neuradaptations to alcohol.
2013-11-06 | GSE49393 | GEO