Placental DNA methylation levels at CYP2E1 and IRS2 are associated with child outcome in a prospective autism study DOI Open Access
Yihui Zhu, Charles E. Mordaunt, Dag H. Yasui

et al.

Human Molecular Genetics, Journal Year: 2019, Volume and Issue: 28(16), P. 2659 - 2674

Published: April 17, 2019

DNA methylation acts at the interface of genetic and environmental factors relevant for autism spectrum disorder (ASD). Placenta, normally discarded birth, is a potentially rich source patterns predictive ASD in child. Here, we performed whole methylome analyses placentas from prospective study MARBLES (Markers Autism Risk Babies-Learning Early Signs) high-risk pregnancies. A total 400 differentially methylated regions (DMRs) discriminated stored children later diagnosed with compared to typically developing controls. These DMRs were significantly enriched promoters, mapped 596 genes functionally neuronal development, overlapped risk. CYP2E1 IRS2 reached genome-wide significance, replicated by pyrosequencing correlated expression differences brain. Methylation associated both diagnosis genotype within DMR. In contrast, was unaffected DMR but modified preconceptional maternal prenatal vitamin use. This therefore identified two useful early epigenetic markers placenta.

Language: Английский

Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder DOI
Ryan K. C. Yuen, Daniele Merico,

Matt Bookman

et al.

Nature Neuroscience, Journal Year: 2017, Volume and Issue: 20(4), P. 602 - 611

Published: March 6, 2017

Language: Английский

Citations

821
Rett syndrome: insights into genetic, molecular and circuit mechanisms DOI
Jacque Pak Kan Ip, Nikolaos Mellios, Mriganka Sur

et al.

Nature reviews. Neuroscience, Journal Year: 2018, Volume and Issue: 19(6), P. 368 - 382

Published: May 8, 2018

Language: Английский

Citations

214
Autism Spectrum Disorder: Neurodevelopmental Risk Factors, Biological Mechanism, and Precision Therapy DOI Open Access
Xuan Wang,

Binquan Wang,

Chunyan Wu

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(3), P. 1819 - 1819

Published: Jan. 17, 2023

Autism spectrum disorder (ASD) is a heterogeneous, behaviorally defined neurodevelopmental disorder. Over the past two decades, prevalence of autism disorders has progressively increased, however, no clear diagnostic markers and specifically targeted medications for have emerged. As result, neurobehavioral abnormalities, neurobiological alterations in ASD, development novel ASD pharmacological therapy necessitate multidisciplinary collaboration. In this review, we discuss multiple animal models to contribute disease mechanisms as well new studies from disciplines assess behavioral pathology ASD. addition, summarize highlight mechanistic advances regarding gene transcription, RNA non-coding translation, abnormal synaptic signaling pathways, epigenetic post-translational modifications, brain-gut axis, immune inflammation neural loop abnormalities provide theoretical basis next step precision therapy. Furthermore, review existing tactics limits present challenges opportunities translating knowledge into clinical practice.

Language: Английский

Citations

106
Methylation across the central dogma in health and diseases: new therapeutic strategies DOI Creative Commons
Ruochen Liu, Erhu Zhao,

Huijuan Yu

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Aug. 24, 2023

The proper transfer of genetic information from DNA to RNA protein is essential for cell-fate control, development, and health. Methylation DNA, RNAs, histones, non-histone proteins a reversible post-synthesis modification that finetunes gene expression function in diverse physiological processes. Aberrant methylation caused by mutations or environmental stimuli promotes various diseases accelerates aging, necessitating the development therapies correct disease-driver imbalance. In this Review, we summarize operating system across central dogma, which includes writers, erasers, readers, reader-independent outputs. We then discuss how dysregulation contributes neurological disorders, cancer, aging. Current small-molecule compounds target modifiers show modest success certain cancers. methylome-wide action lack specificity lead undesirable biological effects cytotoxicity, limiting their therapeutic application, especially with monogenic cause different directions changes. Emerging tools capable site-specific manipulation hold great promise solve dilemma. With refinement delivery vehicles, these new are well positioned advance basic research clinical translation field.

Language: Английский

Citations

56
Understanding environmental contributions to autism: Causal concepts and the state of science DOI Creative Commons
Irva Hertz‐Picciotto, Rebecca J. Schmidt, Paula Krakowiak

et al.

Autism Research, Journal Year: 2018, Volume and Issue: 11(4), P. 554 - 586

Published: March 23, 2018

The complexity of neurodevelopment, the rapidity early neurogenesis, and over 100 years research identifying environmental influences on neurodevelopment serve as backdrop to understanding factors that influence risk severity autism spectrum disorder (ASD). This Keynote Lecture, delivered at May 2016 annual meeting International Society for Autism Research, describes concepts causation, outlines trajectory nongenetic beginning in 1960s, briefly reviews current state this science. Causal are introduced, including root causes; pitfalls interpreting time trends clues etiologic factors; susceptible windows exposure; implications a multi‐factorial model ASD. An historical background presents into origins epidemiologic literature from last fifteen is but critically reviewed potential roles of, example, air pollution, pesticides, plastics, prenatal vitamins, lifestyle family factors, maternal obstetric metabolic conditions during her pregnancy. Three examples case‐control CHildhood Risks Genes Environment Study probed illustrate methodological approaches central challenges observational studies: capturing causal inference when randomized controlled clinical trial either unethical or infeasible; integration genetic, epigenetic, development. We conclude with reflections future directions, exposomics, new technologies, microbiome, gene‐by‐environment interaction era –omics, epigenetics interface those two. As environment malleable, advances goal productive fulfilling life all children, teen‐agers adults. Res 2018, 11: 554–586 . © 2018 Wiley Periodicals, Inc. Lay Summary discusses evidence human studies contributing autism, such nutrition health. There no single cause autism. Examples highlight features high‐quality epidemiology study, what comprises compelling case causation. Emergent directions hold promise interventions reduce disabilities, enhance giftedness, improve lives

Language: Английский

Citations

155
Dysregulation of Cortical Neuron DNA Methylation Profile in Autism Spectrum Disorder DOI Creative Commons
Stefano Nardone,

Dev Sharan Sams,

Antonino Zito

et al.

Cerebral Cortex, Journal Year: 2017, Volume and Issue: 27(12), P. 5739 - 5754

Published: Sept. 6, 2017

Autism Spectrum Disorder (ASD) is a complex neuropsychiatric syndrome whose etiology includes genetic and environmental components. Since epigenetic marks are sensitive to insult, they may be involved in the development of ASD. Initial brain studies have suggested dysregulation However, due cellular heterogeneity brain, these not determined if there true change neuronal signature. Here, we report genome-wide methylation study on fluorescence-activated cell sorting-sorted nuclei from frontal cortex 16 male ASD 15 control subjects. Using 450 K BeadArray, identified 58 differentially methylated regions (DMRs) that included loci associated GABAergic system genes, particularly ABAT GABBR1, brain-specific MicroRNAs. Selected DMRs were validated by targeted Next Generation Bisulfite Sequencing. Weighted gene correlation network analysis detected 3 co-methylation modules which significantly correlated enriched for genomic underlying neuronal, GABAergic, immune genes. Finally, an overlap ASD-related with neurodevelopment DMRs. This investigation identifies alterations DNA pattern cortical neurons, providing further evidence disorder-relevant tissues biology

Language: Английский

Citations

143
Genetic and Epigenetic Etiology Underlying Autism Spectrum Disorder DOI Open Access
Sang Hoon Yoon, Joonhyuk Choi, Won Yong Lee

et al.

Journal of Clinical Medicine, Journal Year: 2020, Volume and Issue: 9(4), P. 966 - 966

Published: March 31, 2020

Autism spectrum disorder (ASD) is a pervasive neurodevelopmental characterized by difficulties in social interaction, language development delays, repeated body movements, and markedly deteriorated activities interests. Environmental factors, such as viral infection, parental age, zinc deficiency, can be plausible contributors to ASD susceptibility. As highly heritable, genetic risk factors involved neurodevelopment, neural communication, interaction provide important clues explaining the etiology of ASD. Accumulated evidence also shows an role epigenetic DNA methylation, histone modification, noncoding RNA, etiology. In this review, we compiled research published date described epidemiology together with environmental underlying different phenotypes

Language: Английский

Citations

126
The Interaction between the Immune System and Epigenetics in the Etiology of Autism Spectrum Disorders DOI Creative Commons
Stefano Nardone, Evan Elliott

Frontiers in Neuroscience, Journal Year: 2016, Volume and Issue: 10

Published: July 11, 2016

Recent studies have firmly established that the etiology of autism includes both genetic and environmental components. However, we are only just beginning to elucidate factors might be involved in development autism, as well molecular mechanisms through which they function. Mounting epidemiological biological evidence suggest prenatal induce a more activated immune state mother autism. In parallel, highlighted role epigenetics brain process susceptible influences potentially causative spectrum disorders (ASD). this review, will discuss converging for multidirectional interaction between system activation during pregnancy epigenetic regulation fetus may cooperate produce an autistic phenotype. This factor-induced changes signatures brain, dysregulation modifications specifically genomic regions encode functions, aberrant microglia. Overall, subsequent developing fetal main consideration cause

Language: Английский

Citations

122
Brain Connectivity and Neuroimaging of Social Networks in Autism DOI
Ralph‐Axel Müller, Inna Fishman

Trends in Cognitive Sciences, Journal Year: 2018, Volume and Issue: 22(12), P. 1103 - 1116

Published: Oct. 31, 2018

Language: Английский

Citations

114
Elevated polygenic burden for autism is associated with differential DNA methylation at birth DOI Creative Commons
Eilís Hannon, Diana Schendel, Christine Ladd‐Acosta

et al.

Genome Medicine, Journal Year: 2018, Volume and Issue: 10(1)

Published: March 28, 2018

Autism spectrum disorder (ASD) is a severe neurodevelopmental characterized by deficits in social communication and restricted, repetitive behaviors, interests, or activities. The etiology of ASD involves both inherited environmental risk factors, with epigenetic processes hypothesized as one mechanism which genetic non-genetic variation influence gene regulation pathogenesis. aim this study was to identify DNA methylation biomarkers detectable at birth. We quantified neonatal methylomic 1263 infants—of whom ~ 50% went on subsequently develop ASD—using isolated from archived blood spots taken shortly after used matched genotype data the same individuals examine molecular consequences ASD-associated variants, identifying associated elevated polygenic burden for ASD. In addition, we performed quantitative trait loci (mQTL) mapping prioritize target genes GWAS findings. identified robust signatures gestational age prenatal tobacco exposure, confirming utility generated spots. Although did not specific showing differences later ASD, there significant association between increased autism loci. Each unit score mean increase − 0.14% two CpG sites located proximal signal chromosome 8. This largest analysis undertaken first integrate demonstrate using disease, mQTL refine functional regulatory variants.

Language: Английский

Citations

110