scholarly journals Analysis of Global and Local DNA Methylation Patterns in Blood Samples of Patients With Autism Spectrum Disorder

2021 ◽  
Vol 9 ◽  
Author(s):  
María Victoria García-Ortiz ◽  
María José de la Torre-Aguilar ◽  
Teresa Morales-Ruiz ◽  
Antonio Gómez-Fernández ◽  
Katherine Flores-Rojas ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Dna Methylation ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Control Group ◽  
Healthy Children ◽  
Blood Samples ◽  
Epigenetic Biomarkers ◽  
Increased Risk ◽  
Methylation Patterns

The goal of this investigation was to determine whether there are alterations in DNA methylation patterns in children with autism spectrum disorder (ASD).Material and Methods: Controlled prospective observational case-control study. Within the ASD group, children were sub-classified based on the presence (AMR subgroup) or absence (ANMR subgroup) of neurodevelopmental regression during the first 2 years of life. We analyzed the global levels of DNA methylation, reflected in LINE-1, and the local DNA methylation pattern in two candidate genes, Neural Cell Adhesion Molecule (NCAM1) and Nerve Growth Factor (NGF) that, according to our previous studies, might be associated to an increased risk for ASD. For this purpose, we utilized blood samples from pediatric patients with ASD (n = 53) and their corresponding controls (n = 45).Results: We observed a slight decrease in methylation levels of LINE-1 in the ASD group, compared to the control group. One of the CpG in LINE-1 (GenBank accession no.X58075, nucleotide position 329) was the main responsible for such reduction, highly significant in the ASD subgroup of children with AMR (p < 0.05). Furthermore, we detected higher NCAM1 methylation levels in ASD children, compared to healthy children (p < 0.001). The data, moreover, showed higher NGF methylation levels in the AMR subgroup, compared to the control group and the ANMR subgroup. These results are consistent with our prior study, in which lower plasma levels of NCAM1 and higher levels of NGF were found in the ANMR subgroup, compared to the subgroup that comprised neurotypically developing children.Conclusions: We have provided new clues about the epigenetic changes that occur in ASD, and suggest two potential epigenetic biomarkers that would facilitate the diagnosis of the disorder. We similarly present with evidence of a clear differentiation in DNA methylation between the ASD subgroups, with or without mental regression.

scholarly journals MOSAIC EPIGENETIC DYSREGULATION OF ECTODERMAL CELLS IN AUTISM SPECTRUM DISORDER

2014 ◽  
Author(s):  
Esther R. Berko ◽  
Masako Suzuki ◽  
Faygel Beren ◽  
Christophe Lemetre ◽  
Christine M. Alaimo ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Dna Methylation ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Dna Mutations ◽  
Genome Wide ◽  
Methylation Assay ◽  
Increased Risk ◽  
Methylation Patterns ◽  
Encoding Protein

DNA mutational events are increasingly being identified in autism spectrum disorder (ASD), but the potential additional role of dysregulation of the epigenome in the pathogenesis of the condition remains unclear. The epigenome is of interest as a possible mediator of environmental effects during development, encoding a cellular memory reflected by altered function of progeny cells. Advanced maternal age (AMA) is associated with an increased risk of having a child with ASD for reasons that are not understood. To explore whether AMA involves covert aneuploidy or epigenetic dysregulation leading to ASD in the offspring, we tested an homogeneous ectodermal cell type from 47 individuals with ASD compared with 48 typically developing (TD) controls born to mothers of ≥35 years, using a quantitative genome-wide DNA methylation assay. We show that DNA methylation patterns are dysregulated in ectodermal cells in these individuals, having accounted for confounding effects due to subject age, sex and ancestral haplotype. We did not find mosaic aneuploidy or copy number variability to occur at differentially-methylated regions in these subjects. Of note, the loci with distinctive DNA methylation were found at genes expressed in the brain and encoding protein products significantly enriched for interactions with those produced by known ASD-causing genes, representing a perturbation by epigenomic dysregulation of the same networks compromised by DNA mutational mechanisms. The results indicate the presence of a mosaic subpopulation of epigenetically-dysregulated, ectodermally-derived cells in subjects with ASD. The epigenetic dysregulation observed in these ASD subjects born to older mothers may be associated with aging parental gametes, environmental influences during embryogenesis or could be the consequence of mutations of the chromatin regulatory genes increasingly implicated in ASD. The results indicate that epigenetic dysregulatory mechanisms may complement and interact with DNA mutations in the pathogenesis of the disorder.

scholarly journals An epigenetic biomarker for adult high-functioning autism spectrum disorder

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Ryo Kimura ◽  
Masatoshi Nakata ◽  
Yasuko Funabiki ◽  
Shiho Suzuki ◽  
Tomonari Awaya ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Dna Methylation ◽  
High Functioning Autism ◽  
Autism Spectrum ◽  
Machine Learning Algorithms ◽  
Spectrum Disorder ◽  
Methylation Array ◽  
High Functioning ◽  
Epigenetic Biomarkers ◽  
Potential Marker

Abstract Increasing evidence suggests that epigenetic mechanisms play a role in the etiology of autism spectrum disorder (ASD). To date, several studies have attempted to identify epigenetic biomarkers for ASD. However, reliable markers remain to be established and most of these studies have focused on pediatric patients with ASD. In this study, we sought to find an epigenetic DNA methylation biomarker from peripheral blood for adult patients with high-functioning ASD. DNA methylation profiles were analyzed using the Illumina 450 K methylation array. To identify robust candidate markers, we employed two types of machine-learning algorithms for marker selection. We identified a potential marker (cg20793532) for which is the AUC value was 0.79. Notably, cg20793532 was annotated to the PPP2R2C gene, which was hypermethylated and down-regulated in blood from ASD patients compared to that in the controls. Although requiring careful interpretation, this pilot study seems to provide a potential blood biomarker for identifying individuals with high-functioning ASD.

scholarly journals Autism spectrum disorder is associated with gut microbiota disorder in children

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Hairong Sun ◽  
Zhong You ◽  
Libo Jia ◽  
Fang Wang
Keyword(s):  
Autism Spectrum Disorder ◽  
Gut Microbiota ◽  
Stable State ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Control Group ◽  
Healthy Children ◽  
16S Sequencing ◽  
Healthy Control ◽  
The Difference

Abstract Background The aim of this study was to evaluate the occurrence and clinical characteristics of autism spectrum disorder (ASD) associated to the stable state of the gut microbiota. Methods A total of 9 children with ASD and 6 healthy children used as control were selected and feces samples were collected from all of them. The 16S gene ribosomal RNA sequencing was used to analyze the difference in gut microbiota between healthy control children and ASD patients. Results The results of 16S sequencing based on operational taxonomic units (OTUs) analysis showed that the ASD group and the healthy control (HC) group had a large difference in the abundance of microbiota at the level of family, genus and species. The abundance of Bacteroidales and Selenomonadales was significantly lower in the ASD group than in the HC group (p = 0.0110 and p = 0.0076, respectively). The abundance of Ruminococcaceae in the ASD group was higher than that in the HC group (p = 0.0285), while the amount of Prevotellaceae was significantly lower in the ASD group than in the HC group (p = 0.0111). The Tax4Fun analysis based on Kyoto Encyclopaedia of Genes and Genomes (KEGG) data indicated differentially expressed functional pathway between the ASD group and healthy control group associated to the nervous system, environmental information processing and cellular processing. Conclusions The abundance of gut microbiota in the ASD group is different from that in the healthy control children. These differences affect the biological function of the host. These results suggest that a disorder in the gut microbiota may be associated, at least in part, with ASD in children.

scholarly journals Impact of MicroRNAs in Interaction With Environmental Factors on Autism Spectrum Disorder: An Exploratory Pilot Study

2021 ◽  
Vol 12 ◽  
Author(s):  
LiHua Cui ◽  
WenRan Du ◽  
Ning Xu ◽  
JingYi Dong ◽  
BingJie Xia ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Environmental Factors ◽  
Neonatal Jaundice ◽  
Maternal Stress ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Control Group ◽  
Psychiatric History ◽  
Healthy Children ◽  
Threatened Abortion

Background: This study aimed to explore the main effects of environmental risk factors as well as their interaction effects with miRNA on the risk of autism spectrum disorder (ASD).Methods: One hundred fifty-nine ASD children (ASD group) and 159 healthy children (control group), aged 2–6 years, were included in this study. ASD diagnoses were based on DSM-5 criteria. The extensive medical and demographic characterization of the two groups were recorded. MicroRNAs (miRNAs) in serum were detected by qRT-PCR.Results: Compared with the control group, the ASD group had significantly higher rates of maternal stress during pregnancy (p < 0.001), maternal drinking during pregnancy (p = 0.006), threatened abortion (p = 0.011), pregnancy-induced hypertension (p = 0.032), gestational diabetes (p = 0.039), maternal anemia during pregnancy (p < 0.001), umbilical cord knot (p < 0.001), neonatal jaundice (p < 0.001), family psychiatric history (p = 0.001), and much lower birth weight (p = 0.012). Furthermore, the ASD group had much lower expression levels of hsa-miR-181b-5p (p < 0.001) and hsa-miR-320a (p < 0.001) and significantly higher levels of hsa-miR-19b-3p (p < 0.001). The interactions of hsa-miR-320a and maternal stress during pregnancy (OR = 39.42, p < 0.001), hsa-miR-19b-3p and neonatal jaundice (OR = 2.44, p < 0.001), and hsa-miR-181b-5p and family psychiatric history (OR = 8.65, p = 0.001) could increase ASD risk.Conclusions: The dysregulation of hsa-miR-181b-5p, hsa-miR-320a, and hsa-miR-19b-3p could interact with environmental factors, such as maternal stress during pregnancy, neonatal jaundice, and family psychiatric history, to impact the risk of ASD.

scholarly journals The urinary biopterin in autism spectrum disorder

Pteridines ◽  
2021 ◽  
Vol 32 (1) ◽  
pp. 17-22
Author(s):  
Aleksandra Waligóra ◽  
Aleksandra Damasiewicz-Bodzek ◽  
Piotr Gorczyca ◽  
Sławomir Waligóra ◽  
Krystyna Tyrpień-Golder
Keyword(s):  
Autism Spectrum Disorder ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
The Other ◽  
Urine Samples ◽  
Control Group ◽  
Healthy Children ◽  
Healthy Individuals ◽  
Children With Asd ◽  
Significant Difference

Abstract Objective The aim of the study was to determine whether biopterin is present in significantly lower quantities in urine samples of patients with autism spectrum disorder (ASD) compared to healthy individuals. Methods The concentration of biopterin in urine samples was measured by ELISA using commercially available kit. The study involved 53 children aged 3–16 years with ASD and 60 healthy children aged 2–14 years. Results Significantly lower biopterin concentration was observed in autistic patients compared to the control group. However, no significant difference was observed between mild, moderate, and severe ASD. Conclusion One of the potential causes of decrease in urinary biopterin levels may be tetrahydrobiopterin (BH4) deficiency, which has extensive and serious health consequences for the nervous system. The results of measuring biopterin as a fully oxidized form of BH4 may suggest that biosynthesis or regeneration of BH4 may be decreased in children with ASD. On the other hand, decreased urinary biopterin levels in children with ASD may be due to BH4 overuse, a good regeneration process, and decreased urinary excretion; and abnormalities in BH4 metabolism appear to be related to the aetiology of ASD or may be due to ASD.

scholarly journals Serum vitamin B12 and folic acid status in Autism spectrum disorder children

2020 ◽  
Vol 14 (2) ◽  
pp. 43-47
Author(s):  
Syeda Nusrat Mahruba ◽  
Shelina Begum ◽  
Shorifa Shahjadi ◽  
Sharmin Afroz ◽  
Umme Raihan Siddiqi ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Folic Acid ◽  
Vitamin B12 ◽  
Neurodevelopmental Disorder ◽  
Serum Vitamin ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Control Group ◽  
P Value ◽  
Healthy Children

Background: Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder. The etiology of ASD involves gene-environmental interaction. Vitamin B12 and folic acid have important roles as methyl donor in many biosynthetic pathways, protein synthesis and formation of myelin sheath throughout the central nervous system. Therefore, deficiency of vitamin B12 and folic acid may act as environmental risk factor for ASD. Objective: To evaluate serum vitamin B12 and folic acid levels in ASD children. Methods: This cross-sectional study was conducted in the Department of Physiology, Bangabandhu Sheikh Mujib Medical University, Shahbag, Dhaka, from 2018 to 2019. Total 100 children 3-10 years of age were enrolled for this study.Among them fifty (50) diagnosed children with ASD were included in the study group. Fifty (50) healthy children constituted the control group. ASD children were selected from the Parent’s Forum for autistic children. No children were included receiving any vitamin supplementation or had acute illness. For this study, serum level of vitamin B12 and folic acid were measured by automated analyzer.For statistical analysis unpaired “t” test and chi square test were done. Result: The mean values of vitamin B12 and folic acid were significantly lower in ASD children than those of control group (p value <0.05). In addition 4% ASD children had vitamin B12 deficiency. Conclusion: Low serum vitamin B12 and folic acid was associated with ASD. J Bangladesh Soc Physiol. 2019, December; 14(2): 43-47

scholarly journals Children with Autism spectrum disorder are associated with gut microbiota disorder

2019 ◽  
Author(s):  
Hairong Sun ◽  
Zhong You ◽  
Libo Jia ◽  
Fang Wang
Keyword(s):  
Autism Spectrum Disorder ◽  
Gut Microbiota ◽  
Stable State ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Control Group ◽  
Healthy Children ◽  
16S Sequencing ◽  
Healthy Control ◽  
The Difference

Abstract Purpose The aim of this study was to evaluate the occurrence and clinical characteristics of autism spectrum disorder (ASD) associated to the stable state of the gut microbiota. Methods A total of 9 children with ASD and 6 healthy children used as control were selected and feces samples were collected from all of them. The 16S gene ribosomal RNA sequencing was used to analyze the difference in gut microbiota between healthy control children and ASD patients. Results The results of 16S sequencing based on operational taxonomic units (OTUs) analysis showed that the ASD group and the healthy control (HC) group had a large difference in the abundance of microbiota at the level of family, genus and species. The abundance of Bacteroidales and Selenomonadales was significantly lower in the ASD group than in the HC group (p=0.0110 and p=0.0076, respectively). The abundance of Ruminococcaceae in the ASD group was higher than that in the HC group (p=0.0265), while the amount of Prevotellaceae was significantly lower in the ASD group than in the HC group (p=0.0265). The Tax4Fun analysis based on Kyoto Encyclopaedia of Genes and Genomes (KEGG) data indicated differentially expressed functional pathway between the ASD group and healthy control group associated to the nervous system, environmental information processing and cellular processing. Conclusions The abundance of gut microbiota in the ASD group is different from that in the healthy control children. These differences affect the biological function of the host. These results suggest that a disorder in the gut microbiota may be associated, at least in part, with ASD in children.

scholarly journals Children with Autism spectrum disorder are associated with gut microbiota disorder

2019 ◽  
Author(s):  
Hairong Sun ◽  
Zhong You ◽  
Libo Jia ◽  
Fang Wang
Keyword(s):  
Autism Spectrum Disorder ◽  
Gut Microbiota ◽  
Stable State ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Control Group ◽  
Healthy Children ◽  
16S Sequencing ◽  
Healthy Control ◽  
The Difference

Abstract Purpose The aim of this study was to evaluate the occurrence and clinical characteristics of autism spectrum disorder (ASD) associated to the stable state of the gut microbiota. Methods A total of 9 children with ASD and 6 healthy children used as control were selected and feces samples were collected from all of them. The 16S gene ribosomal RNA sequencing was used to analyze the difference in gut microbiota between healthy control children and ASD patients. Results The results of 16S sequencing based on operational taxonomic units (OTUs) analysis showed that the ASD group and the healthy control (HC) group had a large difference in the abundance of microbiota at the level of family, genus and species. The abundance of Bacteroidales and Selenomonadales was significantly lower in the ASD group than in the HC group (p=0.0110 and p=0.0076, respectively). The abundance of Ruminococcaceae in the ASD group was higher than that in the HC group (p=0.0265), while the amount of Prevotellaceae was significantly lower in the ASD group than in the HC group (p=0.0265). The Tax4Fun analysis based on Kyoto Encyclopaedia of Genes and Genomes (KEGG) data indicated differentially expressed functional pathway between the ASD group and healthy control group associated to the nervous system, environmental information processing and cellular processing. Conclusions The abundance of gut microbiota in the ASD group is different from that in the healthy control children. These differences affect the biological function of the host. These results suggest that a disorder in the gut microbiota may be associated, at least in part, with ASD in children.

scholarly journals Peripheral blood DNA methylation and autism spectrum disorder

2018 ◽  
Author(s):  
Shan V. Andrews ◽  
Brooke Sheppard ◽  
Gayle C. Windham ◽  
Laura A. Schieve ◽  
Diana E. Schendel ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Dna Methylation ◽  
Sample Size ◽  
Meta Analysis ◽  
Autism Spectrum ◽  
Case Control ◽  
Small Sample ◽  
Spectrum Disorder ◽  
Blood Samples ◽  
Cpg Sites

AbstractBackgroundSeveral reports have suggested a role for epigenetic mechanisms in ASD etiology. Epigenome-wide association studies (EWAS) in autism spectrum disorder (ASD) may shed light on particular biological mechanisms. However, studies of ASD cases versus controls have been limited by post-mortem timing and severely small sample sizes. Reports from in-life sampling of blood or saliva have also been very limited in sample size, and/or genomic coverage. We present the largest case-control EWAS for ASD to date, combining data from population-based case-control and case-sibling pair studies.MethodsDNA from 968 blood samples from children in the Study to Explore Early Development (SEED 1) was used to generate epigenome-wide array DNA methylation (DNAm) data at 485,512 CpG sites for 453 cases and 515 controls, using the Illumina 450K Beadchip. The Simons Simplex Collection (SSC) provided 450K array DNAm data on an additional 343 cases and their unaffected siblings. We performed EWAS meta-analysis across results from the two data sets, with adjustment for sex and surrogate variables that reflect major sources of biological variation and technical confounding such as cell type, batch, and ancestry. We compared top EWAS results to those from a previous brain-based analysis. We also tested for enrichment of ASD EWAS CpGs for being targets of meQTL associations using available SNP genotype data in the SEED sample.FindingsIn this meta-analysis of blood-based DNA from 796 cases and 858 controls, no single CpG met a Bonferroni discovery threshold of p < 1.12×10−7. Seven CpGs showed differences at p < 1×10−5 and 48 at 1×10−4. Of the top 7, 5 showed brain-based ASD associations as well, often with larger effect sizes, and the top 48 overall showed modest concordance (r = 0.31) in direction of effect with cerebellum samples. Finally, we observed suggestive evidence for enrichment of CpG sites controlled by SNPs (meQTL targets) among the EWAS CpGs hits, which was consistent across EWAS and meQTL discovery p-value thresholds.ConclusionsWe report the largest case-control EWAS study of ASD to date. No single CpG site showed a large enough DNAm difference between cases and controls to achieve epigenome-wide significance in this sample size. However, our results suggest the potential to observe disease associations from blood-based samples. Among the 7 sites achieving suggestive statistical significance, we observed consistent, and stronger, effects at the same sites among brain samples. Discovery-oriented EWAS for ASD using blood samples will likely need even larger samples and unified genetic data to further understand DNAm differences in ASD.

scholarly journals Eating Behaviors of Children with Autism—Pilot Study

Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2687
Author(s):  
Anna Brzóska ◽  
Beata Kazek ◽  
Karolina Kozioł ◽  
Agnieszka Kapinos-Gorczyca ◽  
Małgorzata Ferlewicz ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Children With Autism ◽  
Autism Spectrum ◽  
Bottle Feeding ◽  
Spectrum Disorder ◽  
Control Group ◽  
First Year ◽  
Healthy Children ◽  
Autistic Children ◽  
First Year Of Life

Autism Spectrum Disorder (ASD) is the most recognized neuropsychiatric disorder of childhood. Comorbid conditions (such as feeding disorders) are more common among people with autism than among the general population. The most frequent somatic disorders in autistic children include the gastrointestinal disorders observed in 46–91% of patients. The purpose of this study was the evaluation of the nutrition of children with autism, with particular emphasis placed on feeding in the first year of life, in comparison to the group of healthy peers. Participants included 75 Caucasian children (41 children diagnosed with pure autism, and the control group consisting of 34 children without autistic traits). The analysis was performed based on a questionnaire of own design with the first part devoted to the eating practices of the early infancy. Results: Autistic children, as compared to the healthy peers, presented a shortened time of breastfeeding (the children fell asleep at the breast) (p = 0.04), a delayed introduction of dairy products (p = 0.001), the need of more trials to introduce new foods (p = 0.006), a delayed introduction of foods with solid and lumpy structure (p = 0.004), a longer duration of bottle feeding (p = 0.005), delayed attempts to eating using own hands (p = 0.006) and needed a greater support of parents to divert their attention from food during eating (p = 0.05). Conclusions: 1. The dietary problems are more common among children with the autism spectrum disorder than among the population of healthy children, during the first year of life from the time of introducing the complementary foods. 2. The autistic children experience difficulties with eating and require their parents’ additional involvement significantly more often than their healthy peers.

Sign in / Sign up

Export Citation Format

Share Document